Materiały źródłowe

• #1 Porphyria – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/porphyria/symptoms-causes/syc-20356066

  Porphyria (por-FEAR-e-uh) refers to a group of rare disorders that result from a buildup of natural chemicals called porphyrins in the body. […] Eight enzymes are needed to change porphyrins into heme. Without enough of any of these enzymes, porphyrins build up in the body. […] Porphyria is usually inherited. One or both parents pass along a changed gene to their child. […] All types of porphyria involve a problem making heme. Heme is a part of hemoglobin. Hemoglobin is the protein in red blood cells that carries oxygen from the lungs to all parts of the body. Heme also plays a role in clearing drugs and hormones from the body. […] A shortage or change in any of these enzymes causes a buildup of porphyrins. Which enzyme is affected determines the type of porphyria. […] Most forms of porphyria are caused by a gene change passed down from one or both parents. Porphyria can occur if you inherit: A changed gene from one of your parents (autosomal dominant pattern). Changed genes from both parents (autosomal recessive pattern).

• #2 About Porphyria – American Porphyria Foundation

  https://porphyriafoundation.org/for-patients/about-porphyria/

  Porphyria arises as a result of a malfunction in one of the eight steps in the body’s synthesis of a complex molecule called heme. Heme is essential for the transport of oxygen to cells in the body. If any step in the synthesis of heme is blocked, an intermediate chemical accumulates in the cell. Those intermediate chemicals, known as porphyrins or porphyrin precursors, are the substances of which heme is composed. Each type of Porphyria represents a deficiency of a specific enzyme needed for the synthesis of heme. […] The basic defect cannot presently be treated, but significant effort is being directed toward treating the underlying mechanisms that cause symptoms.

• #3 Porphyria – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/porphyria/symptoms-causes/syc-20356066

  Porphyria (por-FEAR-e-uh) refers to a group of rare disorders that result from a buildup of natural chemicals called porphyrins in the body. […] Eight enzymes are needed to change porphyrins into heme. Without enough of any of these enzymes, porphyrins build up in the body. […] Porphyria is usually inherited. One or both parents pass along a changed gene to their child. […] All types of porphyria involve a problem making heme. Heme is a part of hemoglobin. Hemoglobin is the protein in red blood cells that carries oxygen from the lungs to all parts of the body. Heme also plays a role in clearing drugs and hormones from the body. […] A shortage or change in any of these enzymes causes a buildup of porphyrins. Which enzyme is affected determines the type of porphyria. […] Most forms of porphyria are caused by a gene change passed down from one or both parents. Porphyria can occur if you inherit: A changed gene from one of your parents (autosomal dominant pattern). Changed genes from both parents (autosomal recessive pattern).

• #4 Porphyria Information | Mount Sinai – New York

  https://www.mountsinai.org/health-library/diseases-conditions/porphyria

  Porphyrias are a group of rare inherited disorders. An important part of hemoglobin, called heme, is not made properly. […] People with porphyria are lacking certain enzymes needed for this process. This causes abnormal amounts of porphyrins or related chemicals to build up in the body. […] Porphyria is inherited. This means the disorder is passed down through families.

• #5 Porphyria – Wikipedia

  https://en.wikipedia.org/wiki/Porphyria

  Most types of porphyria are inherited from one or both of a person’s parents and are due to a mutation in one of the genes that make heme. […] The underlying mechanism results in a decrease in the amount of heme produced and a build-up of substances involved in making heme. […] The porphyrias are generally considered genetic in nature. […] Subtypes of porphyrias depend on which enzyme is deficient. […] In the autosomal recessive types, anyone who inherit a single gene may become a carrier. Generally they do not have symptoms but may pass the gene on to offspring. […] Some liver diseases may cause porphyria even in the absence of genetic predisposition. These include hemochromatosis and hepatitis C.

• #6 Porphyria: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/porphyria/

  Porphyria is a group of disorders caused by abnormalities in the chemical steps that lead to heme production. […] Researchers have identified several types of porphyria, which are distinguished by their genetic cause and their signs and symptoms. […] Each form of porphyria results from mutations in one of these genes: ALAD, ALAS2, CPOX, FECH, HMBS, PPOX, UROD, or UROS. […] The genes related to porphyria provide instructions for making the enzymes needed to produce heme. Mutations in most of these genes reduce enzyme activity, which limits the amount of heme the body can produce. […] One type of porphyria, porphyria cutanea tarda, results from both genetic and nongenetic factors. […] Many factors contribute to the development of porphyria cutanea tarda. These include an increased amount of iron in the liver, alcohol consumption, smoking, hepatitis C or HIV infection, or certain hormones. […] Mutations in the HFE gene (which cause an iron overload disorder called hemochromatosis) are also associated with porphyria cutanea tarda. […] Other, as-yet-unidentified genetic factors may also play a role in this form of porphyria.

• #7 Porphyria: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/porphyria/

  Porphyria is a group of disorders caused by abnormalities in the chemical steps that lead to heme production. […] Researchers have identified several types of porphyria, which are distinguished by their genetic cause and their signs and symptoms. […] Each form of porphyria results from mutations in one of these genes: ALAD, ALAS2, CPOX, FECH, HMBS, PPOX, UROD, or UROS. […] The genes related to porphyria provide instructions for making the enzymes needed to produce heme. Mutations in most of these genes reduce enzyme activity, which limits the amount of heme the body can produce. […] One type of porphyria, porphyria cutanea tarda, results from both genetic and nongenetic factors. […] Many factors contribute to the development of porphyria cutanea tarda. These include an increased amount of iron in the liver, alcohol consumption, smoking, hepatitis C or HIV infection, or certain hormones. […] Mutations in the HFE gene (which cause an iron overload disorder called hemochromatosis) are also associated with porphyria cutanea tarda. […] Other, as-yet-unidentified genetic factors may also play a role in this form of porphyria.

• #8 Porphyria: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/porphyria/

  Porphyria is a group of disorders caused by abnormalities in the chemical steps that lead to heme production. […] Researchers have identified several types of porphyria, which are distinguished by their genetic cause and their signs and symptoms. […] Each form of porphyria results from mutations in one of these genes: ALAD, ALAS2, CPOX, FECH, HMBS, PPOX, UROD, or UROS. […] The genes related to porphyria provide instructions for making the enzymes needed to produce heme. Mutations in most of these genes reduce enzyme activity, which limits the amount of heme the body can produce. […] One type of porphyria, porphyria cutanea tarda, results from both genetic and nongenetic factors. […] Many factors contribute to the development of porphyria cutanea tarda. These include an increased amount of iron in the liver, alcohol consumption, smoking, hepatitis C or HIV infection, or certain hormones. […] Mutations in the HFE gene (which cause an iron overload disorder called hemochromatosis) are also associated with porphyria cutanea tarda. […] Other, as-yet-unidentified genetic factors may also play a role in this form of porphyria.

• #9 Porphyria Overview: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1389981-overview

  Porphyria is the common term for a group of syndromes, largely hereditary, that result from defects in porphyrins (the enzymes involved in heme synthesis). Depending on the specific enzyme affected, porphyria may manifest clinically in an acute or non-acute manner, and the signs and symptoms may be predominantly neurovisceral, psychiatric, cutaneous, or some combination of those. […] Porphyrias can be inherited or (rarely) acquired. There are at least 8 different types of porphyrias. Acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), variegate porphyria (VP), and the familial form of porphyria cutanea tarda (PCT) follow an autosomal dominant inheritance pattern with low penetration. Aminolevulinic acid dehydratase deficiency porphyria (ADP), congenital erythropoietic porphyria (CEP), erythropoietic protoporphyria (EPP), and hepatoerythropoietic porphyria (HEP) are autosomal recessive. There is also an X-linked dominant inherited porphyria called X-linked protoporphyria (XLP).

• #10 Porphyria – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/porphyria/symptoms-causes/syc-20356066

  Porphyria (por-FEAR-e-uh) refers to a group of rare disorders that result from a buildup of natural chemicals called porphyrins in the body. […] Eight enzymes are needed to change porphyrins into heme. Without enough of any of these enzymes, porphyrins build up in the body. […] Porphyria is usually inherited. One or both parents pass along a changed gene to their child. […] All types of porphyria involve a problem making heme. Heme is a part of hemoglobin. Hemoglobin is the protein in red blood cells that carries oxygen from the lungs to all parts of the body. Heme also plays a role in clearing drugs and hormones from the body. […] A shortage or change in any of these enzymes causes a buildup of porphyrins. Which enzyme is affected determines the type of porphyria. […] Most forms of porphyria are caused by a gene change passed down from one or both parents. Porphyria can occur if you inherit: A changed gene from one of your parents (autosomal dominant pattern). Changed genes from both parents (autosomal recessive pattern).

• #11 Porphyria: Types, Causes, and Treatment

  https://patient.info/allergies-blood-immune/porphyria-leaflet

  The porphyrias are a group of disorders in which there is a problem with the production of haem (also spelled heme) within the body. […] Most types of porphyria are inherited. That is, they are passed on in families through the genes. If you inherit a faulty gene you can develop porphyria. […] However, in many people there may be no family history. In these cases it can be triggered in susceptible people by exposure to certain medicines or chemicals, including oral contraceptives and alcohol. […] Most types of inherited porphyria are passed on in families through what is called autosomal dominant inheritance. Briefly, this means that if you have porphyria (and therefore a gene that is faulty), each child that you have has a 50:50 chance of inheriting the faulty gene and also developing the condition.

• #12 Porphyria – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/porphyria/symptoms-causes/syc-20356066

  Porphyria (por-FEAR-e-uh) refers to a group of rare disorders that result from a buildup of natural chemicals called porphyrins in the body. […] Eight enzymes are needed to change porphyrins into heme. Without enough of any of these enzymes, porphyrins build up in the body. […] Porphyria is usually inherited. One or both parents pass along a changed gene to their child. […] All types of porphyria involve a problem making heme. Heme is a part of hemoglobin. Hemoglobin is the protein in red blood cells that carries oxygen from the lungs to all parts of the body. Heme also plays a role in clearing drugs and hormones from the body. […] A shortage or change in any of these enzymes causes a buildup of porphyrins. Which enzyme is affected determines the type of porphyria. […] Most forms of porphyria are caused by a gene change passed down from one or both parents. Porphyria can occur if you inherit: A changed gene from one of your parents (autosomal dominant pattern). Changed genes from both parents (autosomal recessive pattern).

• #13 Overview of Porphyrias – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/the-porphyrias/overview-of-porphyrias

  In the autosomal recessive porphyrias, only homozygous or compound heterozygous states cause disease. […] X-linked inheritance occurs in one of the porphyrias, X-linked protoporphyria (XLP), in which there are gain-of-function mutations, usually deletions in exon 11 of the gene ALAS2. […] X-linked protoporphyria results from gain-of-function mutations that increase the activity of ALAS 2, causing accumulation of protoporphyrin.

• #14 Overview of Porphyrias – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/the-porphyrias/overview-of-porphyrias

  In the autosomal recessive porphyrias, only homozygous or compound heterozygous states cause disease. […] X-linked inheritance occurs in one of the porphyrias, X-linked protoporphyria (XLP), in which there are gain-of-function mutations, usually deletions in exon 11 of the gene ALAS2. […] X-linked protoporphyria results from gain-of-function mutations that increase the activity of ALAS 2, causing accumulation of protoporphyrin.

• #15 Causes of PorphyriasEnvelope icon

  https://porphyrianews.com/causes-of-porphyrias/

  Porphyrias are a group of genetic disorders that are caused by disruptions in heme production. […] Each type of porphyria stems from the loss of a specific enzyme necessary for heme production. […] Porphyrias result from the combination of genetic and environmental triggers. […] The genetic mutations associated with porphyrias — often considered more as predisposing factors than outright causes — can be inherited in one of three manners: autosomal recessive, autosomal dominant, or X-linked. […] Although inherited genetic mutations underlie all porphyrias, not everyone carrying these mutations will experience symptoms. […] Common triggers for porphyrias include excessive alcohol consumption, sunlight exposure, use of certain medications, stress, and fasting. […] The extremely rare X-linked protoporphyria (XLP) arises from mutations in the ALAS2 gene.

• #16 Overview of Porphyrias – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/the-porphyrias/overview-of-porphyrias

  Porphyrias are rare disorders in which there are defects in the pathway of heme synthesis, in all but one type (X-linked protoporphyria), due to genetic or acquired deficiencies of enzymes of the heme biosynthetic pathway. […] With the exception of the sporadic type of porphyria cutanea tarda (PCT, which also has an inherited type), the porphyrias are inherited diseases. Autosomal dominant inheritance is most common. […] In the autosomal dominant porphyrias, homozygous or compound heterozygous states (ie, 2 separate heterozygous mutations, one in each allele of the same gene in the same patient) may be incompatible with life, typically causing fetal death. […] The prevalence of the causative genetic mutation for AIP is about 1/1500, but because penetrance is low, the prevalence of clinical disease is also about 1/10,000.

• #17 Overview of Porphyrias – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/the-porphyrias/overview-of-porphyrias

  In the autosomal recessive porphyrias, only homozygous or compound heterozygous states cause disease. […] X-linked inheritance occurs in one of the porphyrias, X-linked protoporphyria (XLP), in which there are gain-of-function mutations, usually deletions in exon 11 of the gene ALAS2. […] X-linked protoporphyria results from gain-of-function mutations that increase the activity of ALAS 2, causing accumulation of protoporphyrin.

• #18 Porphyria – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/porphyria/symptoms-causes/syc-20356066

  Porphyria (por-FEAR-e-uh) refers to a group of rare disorders that result from a buildup of natural chemicals called porphyrins in the body. […] Eight enzymes are needed to change porphyrins into heme. Without enough of any of these enzymes, porphyrins build up in the body. […] Porphyria is usually inherited. One or both parents pass along a changed gene to their child. […] All types of porphyria involve a problem making heme. Heme is a part of hemoglobin. Hemoglobin is the protein in red blood cells that carries oxygen from the lungs to all parts of the body. Heme also plays a role in clearing drugs and hormones from the body. […] A shortage or change in any of these enzymes causes a buildup of porphyrins. Which enzyme is affected determines the type of porphyria. […] Most forms of porphyria are caused by a gene change passed down from one or both parents. Porphyria can occur if you inherit: A changed gene from one of your parents (autosomal dominant pattern). Changed genes from both parents (autosomal recessive pattern).

• #19 Acute Porphyria – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK537352/

  Acute porphyrias are genetic conditions; however, environmental, e.g., drugs and physiological factors, are crucial for clinical manifestation. […] Porphyria is a genetic disorder. […] More than 100 mutations have been identified. […] Clinical manifestation is associated with a 50% or more reduction in enzyme function. […] Hereditary coproporphyria is caused by significant heterogeneity and abnormal functioning of coproporphyrinogen oxidase. […] A 50% reduction in protoporphyrinogen oxidase is present in all the samples tested. […] The pathogenesis of neurovisceral symptoms in acute porphyria has not been fully elucidated. […] The enzyme affected is porphobilinogen (PBG) deaminase also referred to as Hydroxymethylbilane synthase (HMBS). […] The rarest acute porphyria, which is caused by a defect in the enzyme ALA dehydratase, is known as delta-aminolevulinic aciduria or ALA dehydratase deficiency (ALAD) and has an autosomal recessive inheritance pattern.

• #20 Acute Porphyria – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK537352/

  Acute porphyrias are genetic conditions; however, environmental, e.g., drugs and physiological factors, are crucial for clinical manifestation. […] Porphyria is a genetic disorder. […] More than 100 mutations have been identified. […] Clinical manifestation is associated with a 50% or more reduction in enzyme function. […] Hereditary coproporphyria is caused by significant heterogeneity and abnormal functioning of coproporphyrinogen oxidase. […] A 50% reduction in protoporphyrinogen oxidase is present in all the samples tested. […] The pathogenesis of neurovisceral symptoms in acute porphyria has not been fully elucidated. […] The enzyme affected is porphobilinogen (PBG) deaminase also referred to as Hydroxymethylbilane synthase (HMBS). […] The rarest acute porphyria, which is caused by a defect in the enzyme ALA dehydratase, is known as delta-aminolevulinic aciduria or ALA dehydratase deficiency (ALAD) and has an autosomal recessive inheritance pattern.

• #21 Acute Porphyria – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK537352/

  Acute porphyrias are genetic conditions; however, environmental, e.g., drugs and physiological factors, are crucial for clinical manifestation. […] Porphyria is a genetic disorder. […] More than 100 mutations have been identified. […] Clinical manifestation is associated with a 50% or more reduction in enzyme function. […] Hereditary coproporphyria is caused by significant heterogeneity and abnormal functioning of coproporphyrinogen oxidase. […] A 50% reduction in protoporphyrinogen oxidase is present in all the samples tested. […] The pathogenesis of neurovisceral symptoms in acute porphyria has not been fully elucidated. […] The enzyme affected is porphobilinogen (PBG) deaminase also referred to as Hydroxymethylbilane synthase (HMBS). […] The rarest acute porphyria, which is caused by a defect in the enzyme ALA dehydratase, is known as delta-aminolevulinic aciduria or ALA dehydratase deficiency (ALAD) and has an autosomal recessive inheritance pattern.

• #22 Acute Intermittent Porphyria (AIP) – American Porphyria Foundation

  https://porphyriafoundation.org/for-patients/types-of-porphyria/aip/

  Acute Intermittent Porphyria (AIP) is a rare metabolic disorder that is characterized by deficiency of the enzyme hydroxymethylbilane synthase (HMBS), also known as porphobilinogen deaminase (PBGD). This enzyme deficiency can result in the accumulation of toxic porphyrin precursors in the body. […] The PBGD enzyme deficiency is caused by a mutation in the HMBS gene which is inherited as an autosomal dominant trait (only one HMBS gene copy is affected). However, the majority of people with a mutation in this gene do not develop symptoms of AIP; additional factors, often called “triggers” are also required to cause symptomatic acute Porphyria. […] AIP is a multifactorial disorder, which means that several different factors such as genetic and environmental factors occurring in combination are necessary for developing symptoms of the disorder.

• #23 Porphyria Overview: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1389981-overview

  The mutations that underlie porphyria result in accumulation and increased excretion of porphyrins and their precursors. Clinical manifestations depend on the step in the heme production pathway in which the enzymatic defect occurs. […] In both type I and type II PCT, clinical expression most often follows exposure to environmental hepatotoxins, such as polyhalogenated aromatic hydrocarbons or ethanol, or to infectious agents such as hepatitis C virus (HCV). […] Hepatoerythropoietic porphyria is a rare autosomal recessive disease that results from severely deficient UROD activity due to the mutation of both UROD alleles (homozygosity or compound heterozygosity). […] In porphyria cutanea tarda (PCT) and hepatoerythropoietic porphyria (HEP), the enzyme uroporphyrinogen decarboxylase is deficient and it leads to a buildup of porphyrias and precursors that spill out of the liver and accumulate in other parts of the body, such as skin, urine, and stool.

• #24 Porphyria cutanea tarda: Causes, symptoms, and diagnosis

  https://www.medicalnewstoday.com/articles/318543

  Porphyria cutanea tarda (PCT) is the most common form of porphyria but is still rare, affecting only 1 in every 10,000 to 25,000 people in the general population. […] PCT is a cutaneous porphyria caused by a deficiency of the enzyme uroporphyrinogen decarboxylase (UROD), which helps convert porphyrins into heme. […] PCT occurs when the body’s ability to make UROD is interrupted. […] PCT can be caused by hepatitis C, HIV, and excessive alcohol consumption. […] A minority of people with the condition have familial PCT, which means the UROD deficiency is genetic.

• #25 Causes of PorphyriasEnvelope icon

  https://porphyrianews.com/causes-of-porphyrias/

  Mutations in the ALAD gene that prevent this step from happening underlie the autosomal recessive ALAD porphyria. […] Acute intermittent porphyria (AIP) — an autosomal dominant form of porphyria — occurs when mutations in the associated HMBS gene interfere with this enzyme’s function. […] Mutations in UROS and GATA1 genes underlie congenital erythropoietic porphyria (CEP), one of the rarest forms of porphyria. […] Mutations in the UROD gene cause familial porphyria cutanea tarda (PCT), a rarer subtype of PCT, which is the most common form of porphyria. […] UROD mutations also may cause the autosomal recessive hepatoerythropoietic porphyria (HEP). […] Mutations in the CPOX gene, which encodes this enzyme, predispose people to hereditary coproporphyria (HCP). […] Disease-causing mutations in PPOX, the gene that provides instructions to make the protoporphyrinogen oxidase enzyme, can result in variegate porphyria (VP). […] Finally, mutations in the FECH gene cause a deficiency in ferrochelatase, the enzyme needed in the last step of heme production, resulting in erythropoietic protoporphyria (EPP).

• #26 Variegate porphyria

  https://dermnetnz.org/topics/variegate-porphyria

  Variegate porphyria is caused by a gene mutation of the protoporphyrinogen oxidase enzyme protein (PPOX). This enzyme is critical in the chemical process that leads to haem production. […] In people with variegate porphyria activity of the PPOX enzyme is reduced by 50%. This means there is as build-up of toxic porphyrins particularly uroporphyrin and coproprophyrin, which leads to blistering. […] Variegate porphyria is an autosomal dominant disorder. This means that a male or female carrying the gene will pass it on to half of his or her children. […] In most people with variegate porphyria signs and symptoms may only become apparent when they are exposed to non-genetic factors such as certain drugs, stress, dieting or fasting, and certain hormones. These factors increase the demand for haem and the enzymes to make haem. The combinations of increased demand and reduced activity of PPOX disrupts haem production and triggers an acute variegate porphyria attack.

• #27 Causes of PorphyriasEnvelope icon

  https://porphyrianews.com/causes-of-porphyrias/

  Mutations in the ALAD gene that prevent this step from happening underlie the autosomal recessive ALAD porphyria. […] Acute intermittent porphyria (AIP) — an autosomal dominant form of porphyria — occurs when mutations in the associated HMBS gene interfere with this enzyme’s function. […] Mutations in UROS and GATA1 genes underlie congenital erythropoietic porphyria (CEP), one of the rarest forms of porphyria. […] Mutations in the UROD gene cause familial porphyria cutanea tarda (PCT), a rarer subtype of PCT, which is the most common form of porphyria. […] UROD mutations also may cause the autosomal recessive hepatoerythropoietic porphyria (HEP). […] Mutations in the CPOX gene, which encodes this enzyme, predispose people to hereditary coproporphyria (HCP). […] Disease-causing mutations in PPOX, the gene that provides instructions to make the protoporphyrinogen oxidase enzyme, can result in variegate porphyria (VP). […] Finally, mutations in the FECH gene cause a deficiency in ferrochelatase, the enzyme needed in the last step of heme production, resulting in erythropoietic protoporphyria (EPP).

• #28 Acute Porphyria – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK537352/

  Acute porphyrias are genetic conditions; however, environmental, e.g., drugs and physiological factors, are crucial for clinical manifestation. […] Porphyria is a genetic disorder. […] More than 100 mutations have been identified. […] Clinical manifestation is associated with a 50% or more reduction in enzyme function. […] Hereditary coproporphyria is caused by significant heterogeneity and abnormal functioning of coproporphyrinogen oxidase. […] A 50% reduction in protoporphyrinogen oxidase is present in all the samples tested. […] The pathogenesis of neurovisceral symptoms in acute porphyria has not been fully elucidated. […] The enzyme affected is porphobilinogen (PBG) deaminase also referred to as Hydroxymethylbilane synthase (HMBS). […] The rarest acute porphyria, which is caused by a defect in the enzyme ALA dehydratase, is known as delta-aminolevulinic aciduria or ALA dehydratase deficiency (ALAD) and has an autosomal recessive inheritance pattern.

• #29 Causes of PorphyriasEnvelope icon

  https://porphyrianews.com/causes-of-porphyrias/

  Mutations in the ALAD gene that prevent this step from happening underlie the autosomal recessive ALAD porphyria. […] Acute intermittent porphyria (AIP) — an autosomal dominant form of porphyria — occurs when mutations in the associated HMBS gene interfere with this enzyme’s function. […] Mutations in UROS and GATA1 genes underlie congenital erythropoietic porphyria (CEP), one of the rarest forms of porphyria. […] Mutations in the UROD gene cause familial porphyria cutanea tarda (PCT), a rarer subtype of PCT, which is the most common form of porphyria. […] UROD mutations also may cause the autosomal recessive hepatoerythropoietic porphyria (HEP). […] Mutations in the CPOX gene, which encodes this enzyme, predispose people to hereditary coproporphyria (HCP). […] Disease-causing mutations in PPOX, the gene that provides instructions to make the protoporphyrinogen oxidase enzyme, can result in variegate porphyria (VP). […] Finally, mutations in the FECH gene cause a deficiency in ferrochelatase, the enzyme needed in the last step of heme production, resulting in erythropoietic protoporphyria (EPP).

• #30 Acute Porphyria – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK537352/

  Acute porphyrias are genetic conditions; however, environmental, e.g., drugs and physiological factors, are crucial for clinical manifestation. […] Porphyria is a genetic disorder. […] More than 100 mutations have been identified. […] Clinical manifestation is associated with a 50% or more reduction in enzyme function. […] Hereditary coproporphyria is caused by significant heterogeneity and abnormal functioning of coproporphyrinogen oxidase. […] A 50% reduction in protoporphyrinogen oxidase is present in all the samples tested. […] The pathogenesis of neurovisceral symptoms in acute porphyria has not been fully elucidated. […] The enzyme affected is porphobilinogen (PBG) deaminase also referred to as Hydroxymethylbilane synthase (HMBS). […] The rarest acute porphyria, which is caused by a defect in the enzyme ALA dehydratase, is known as delta-aminolevulinic aciduria or ALA dehydratase deficiency (ALAD) and has an autosomal recessive inheritance pattern.

• #31 Causes of PorphyriasEnvelope icon

  https://porphyrianews.com/causes-of-porphyrias/

  Mutations in the ALAD gene that prevent this step from happening underlie the autosomal recessive ALAD porphyria. […] Acute intermittent porphyria (AIP) — an autosomal dominant form of porphyria — occurs when mutations in the associated HMBS gene interfere with this enzyme’s function. […] Mutations in UROS and GATA1 genes underlie congenital erythropoietic porphyria (CEP), one of the rarest forms of porphyria. […] Mutations in the UROD gene cause familial porphyria cutanea tarda (PCT), a rarer subtype of PCT, which is the most common form of porphyria. […] UROD mutations also may cause the autosomal recessive hepatoerythropoietic porphyria (HEP). […] Mutations in the CPOX gene, which encodes this enzyme, predispose people to hereditary coproporphyria (HCP). […] Disease-causing mutations in PPOX, the gene that provides instructions to make the protoporphyrinogen oxidase enzyme, can result in variegate porphyria (VP). […] Finally, mutations in the FECH gene cause a deficiency in ferrochelatase, the enzyme needed in the last step of heme production, resulting in erythropoietic protoporphyria (EPP).

• #32 Causes of PorphyriasEnvelope icon

  https://porphyrianews.com/causes-of-porphyrias/

  Mutations in the ALAD gene that prevent this step from happening underlie the autosomal recessive ALAD porphyria. […] Acute intermittent porphyria (AIP) — an autosomal dominant form of porphyria — occurs when mutations in the associated HMBS gene interfere with this enzyme’s function. […] Mutations in UROS and GATA1 genes underlie congenital erythropoietic porphyria (CEP), one of the rarest forms of porphyria. […] Mutations in the UROD gene cause familial porphyria cutanea tarda (PCT), a rarer subtype of PCT, which is the most common form of porphyria. […] UROD mutations also may cause the autosomal recessive hepatoerythropoietic porphyria (HEP). […] Mutations in the CPOX gene, which encodes this enzyme, predispose people to hereditary coproporphyria (HCP). […] Disease-causing mutations in PPOX, the gene that provides instructions to make the protoporphyrinogen oxidase enzyme, can result in variegate porphyria (VP). […] Finally, mutations in the FECH gene cause a deficiency in ferrochelatase, the enzyme needed in the last step of heme production, resulting in erythropoietic protoporphyria (EPP).

• #33 Porphyria

  https://www.pediatriconcall.com/articles/genetics/porphyria/porphyria-introduction

  Most of the patients who inherit the disorder enjoy normal health, However, they are at risk of developing an attack if exposed to various precipitating factors such as alcohol, infection, dieting, and drugs. […] The drugs commonly causing the acute attack are: Diuretics like frusemide, hydrochlorothiazide […] Antihypertensives like Alpha Methyl Dopa, Enalapril, Hydralazine, Lisinopril, Nifedipine, Verapamil […] Antihistamines like Dimenhydrinate, Terfenadine. […] Hypnotics like Amylobarbitone, Diazepam, Flurazepam. […] Anticonvulsants like Barbiturates, carbamazepine, ethosuximide, Hydantoins, Phenytoin. […] Antibiotics: Chloramphenicol, Erythromycin, Cloxacillin, Griseofulvin, Pyrazinamide, Sulphonamides. […] Miscellaneous-Oral contraceptives, Sulphonylureas, Ergotamine. […] Skin problems in porphyria are usually acquired conditions. Patients with VP, HC, CP, and PCT have very sensitive skin, which is easily damaged. […] Long term, their skin becomes thin, dark, scarred, and often hairy. […] There is no cure for porphyria. However, it can be made less severe. Patients with PCT should avoid alcohol.

• #34 Porphyria – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/porphyria/symptoms-causes/syc-20356066

  Just because you inherit a gene or genes that can cause porphyria doesn’t mean that you’ll have symptoms. You might never have symptoms. This also is the case for most carriers of the changed genes. […] Porphyria cutanea tarda (PCT) usually is not passed down in families. In PCT, certain triggers can cause a buildup of porphyrins that may cause symptoms. Examples of triggers include: Too much iron in the body, often due to a condition called hemochromatosis, which is caused by a gene change. Viral infections, such as HIV or hepatitis C. Heavy alcohol use. Smoking. Hormones changes during the menstrual period. […] In addition to genetic risk factors, environmental risk factors may trigger symptoms in porphyria. When exposed to the trigger, the body’s demand for heme production increases. This overwhelms the low level of a needed enzyme, setting in motion a process that causes a buildup of porphyrins.

• #35 What Is Porphyria? Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/17760-porphyria

  Porphyria refers to a group of disorders (often genetic) that affect your nervous system and/or skin. […] Porphyria is often inherited. This means a gene change affecting heme production can be passed down within biological families, putting other family members at risk of also developing porphyria or being disease carriers. […] Changes in certain genes cause acute porphyria. But just because you inherit a gene change doesnt mean youll develop symptoms of porphyria. […] Experts think other factors, like hormones, medications and things you eat or drink, play an important role in causing acute attacks. […] PCT occurs mostly in adults and is one type of porphyria thats a bit different. It often has what providers call acquired causes. This means you can develop this condition even if you dont inherit a gene change.

• #36 Acute Intermittent Porphyria (AIP) – American Porphyria Foundation

  https://porphyriafoundation.org/for-patients/types-of-porphyria/aip/

  Acute Intermittent Porphyria (AIP) is a rare metabolic disorder that is characterized by deficiency of the enzyme hydroxymethylbilane synthase (HMBS), also known as porphobilinogen deaminase (PBGD). This enzyme deficiency can result in the accumulation of toxic porphyrin precursors in the body. […] The PBGD enzyme deficiency is caused by a mutation in the HMBS gene which is inherited as an autosomal dominant trait (only one HMBS gene copy is affected). However, the majority of people with a mutation in this gene do not develop symptoms of AIP; additional factors, often called “triggers” are also required to cause symptomatic acute Porphyria. […] AIP is a multifactorial disorder, which means that several different factors such as genetic and environmental factors occurring in combination are necessary for developing symptoms of the disorder.

• #37 Porphyria – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/porphyria/symptoms-causes/syc-20356066

  Just because you inherit a gene or genes that can cause porphyria doesn’t mean that you’ll have symptoms. You might never have symptoms. This also is the case for most carriers of the changed genes. […] Porphyria cutanea tarda (PCT) usually is not passed down in families. In PCT, certain triggers can cause a buildup of porphyrins that may cause symptoms. Examples of triggers include: Too much iron in the body, often due to a condition called hemochromatosis, which is caused by a gene change. Viral infections, such as HIV or hepatitis C. Heavy alcohol use. Smoking. Hormones changes during the menstrual period. […] In addition to genetic risk factors, environmental risk factors may trigger symptoms in porphyria. When exposed to the trigger, the body’s demand for heme production increases. This overwhelms the low level of a needed enzyme, setting in motion a process that causes a buildup of porphyrins.

• #38 Porphyria: Types, Symptoms, and Treatment

  https://www.healthline.com/health/porphyria

  Porphyria is a genetic disease. According to the National Institutes of Health (NIH), most types of porphyria are inherited from an abnormal gene, called a gene mutation, from one parent. […] However, certain factors may trigger symptoms of porphyria, known as attacks. Factors include: use of certain medications, use of hormones, such as estrogen, alcohol use, smoking, infection, exposure to sunlight, stress, dieting and fasting.

• #39 Porphyria Cutanea Tarda – Hormonal and Metabolic Disorders – MSD Manual Consumer Version

  https://www.msdmanuals.com/home/hormonal-and-metabolic-disorders/the-porphyrias/porphyria-cutanea-tarda

  Porphyria cutanea tarda is the most common porphyria and causes blistering and fragility of skin exposed to sunlight. […] Porphyria cutanea tarda results from underactivity of the enzyme uroporphyrinogen decarboxylase, which leads to accumulation of porphyrins in the liver. […] These factors are thought to interact with iron and oxygen in the liver and thereby inhibit or damage the enzyme uroporphyrinogen decarboxylase. […] Hepatitis C infection is a major risk factor for development of porphyria cutanea tarda, and it should be looked for in all patients with this disorder. […] As far as is known, the sporadic form of this porphyria is the only porphyria that can occur in people who do not have an inherited deficiency of an enzyme involved in heme production.

• #40 Acute Hepatic Porphyria: Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/24112-acute-hepatic-porphyria

  Acute hepatic porphyria (AHP) is a group of rare genetic disorders that begin in your liver and go on to affect your nervous system, causing symptoms throughout your body. […] Porphyria is a deficiency in one of the enzymes that your body needs to make heme (a component of hemoglobin in your blood). During the process of making heme, the absence of specific enzymes causes other compounds to go unused and build up in your body tissues. These leftover compounds called porphyrin precursors are toxic when they build up. In acute hepatic porphyria, they build up in your liver first. […] Genetic mutations are the original cause of AHP, but having the gene mutation isn’t usually enough to trigger the onset of symptoms. Most commonly, hormone changes in puberty trigger them for the first time. Other factors that can trigger them are prescription and recreational drug use, excessive alcohol use, severe calorie restriction and illnesses that cause significant stress to your metabolic system.

• #41 Porphyria | Better Health Channel

  https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/porphyria

  Porphyria occurs when the body cannot convert compounds called porphyrins into heme. […] In most cases, a combination of genetic and environmental factors trigger porphyria symptoms. […] Most forms of porphyria are inherited. This means the genetic predisposition for the condition is passed from one generation to the next. […] Not everyone who has the altered gene will develop porphyria. It appears that an environmental trigger is needed for porphyria to develop. […] Common triggers include prescription drugs such as barbiturates, tranquillisers, sedatives, oral contraceptives and some types of antibiotics.

• #42 Acute Porphyrias – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/the-porphyrias/acute-porphyrias

  Other factors include medications, particularly those that induce hepatic ALA synthase-1 and cytochrome P-450 enzymes. […] A minority of patients with acute hepatic porphyrias also develop acute pancreatitis, for which alternative potential causes, such as gallstones, excess alcohol use, and severe hypertriglyceridemia, are not found. […] Chronic kidney disease in acute porphyria is multifactorial; acute hypertension (possibly leading to chronic hypertension) is likely a main precipitating factor. However, genetic factors, especially a genetic variation in the peptide transporter 2 (PEPT2) gene, which encodes a peptide and amino acid transporter that can affect reabsorption of ALA in the proximal tubule, have been found in patients with acute intermittent porphyria who have developed chronic kidney disease.

• #43 Porphyria – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/porphyria/symptoms-causes/syc-20356066

  Just because you inherit a gene or genes that can cause porphyria doesn’t mean that you’ll have symptoms. You might never have symptoms. This also is the case for most carriers of the changed genes. […] Porphyria cutanea tarda (PCT) usually is not passed down in families. In PCT, certain triggers can cause a buildup of porphyrins that may cause symptoms. Examples of triggers include: Too much iron in the body, often due to a condition called hemochromatosis, which is caused by a gene change. Viral infections, such as HIV or hepatitis C. Heavy alcohol use. Smoking. Hormones changes during the menstrual period. […] In addition to genetic risk factors, environmental risk factors may trigger symptoms in porphyria. When exposed to the trigger, the body’s demand for heme production increases. This overwhelms the low level of a needed enzyme, setting in motion a process that causes a buildup of porphyrins.

• #44 Acute Hepatic Porphyria: Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/24112-acute-hepatic-porphyria

  Acute hepatic porphyria (AHP) is a group of rare genetic disorders that begin in your liver and go on to affect your nervous system, causing symptoms throughout your body. […] Porphyria is a deficiency in one of the enzymes that your body needs to make heme (a component of hemoglobin in your blood). During the process of making heme, the absence of specific enzymes causes other compounds to go unused and build up in your body tissues. These leftover compounds called porphyrin precursors are toxic when they build up. In acute hepatic porphyria, they build up in your liver first. […] Genetic mutations are the original cause of AHP, but having the gene mutation isn’t usually enough to trigger the onset of symptoms. Most commonly, hormone changes in puberty trigger them for the first time. Other factors that can trigger them are prescription and recreational drug use, excessive alcohol use, severe calorie restriction and illnesses that cause significant stress to your metabolic system.

• #45 Porphyria – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/porphyria/symptoms-causes/syc-20356066

  Just because you inherit a gene or genes that can cause porphyria doesn’t mean that you’ll have symptoms. You might never have symptoms. This also is the case for most carriers of the changed genes. […] Porphyria cutanea tarda (PCT) usually is not passed down in families. In PCT, certain triggers can cause a buildup of porphyrins that may cause symptoms. Examples of triggers include: Too much iron in the body, often due to a condition called hemochromatosis, which is caused by a gene change. Viral infections, such as HIV or hepatitis C. Heavy alcohol use. Smoking. Hormones changes during the menstrual period. […] In addition to genetic risk factors, environmental risk factors may trigger symptoms in porphyria. When exposed to the trigger, the body’s demand for heme production increases. This overwhelms the low level of a needed enzyme, setting in motion a process that causes a buildup of porphyrins.

• #46 Porphyria Cutanea Tarda: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1103643-overview

  A strong association between PCT and hereditary hemochromatosis genes causing hepatic siderosis has been established. […] Hepatitis virus infections are frequently associated with PCT. […] Tobacco smoking is a behavioral characteristic frequently observed among patients with PCT. […] Environmental exposure to aromatic polyhalogenated hepatotoxins also induces hepatic cytochromes, thus potentiating production of oxidation products capable of inhibiting UROD activity.

• #47 Porphyria – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/porphyria/symptoms-causes/syc-20356066

  Just because you inherit a gene or genes that can cause porphyria doesn’t mean that you’ll have symptoms. You might never have symptoms. This also is the case for most carriers of the changed genes. […] Porphyria cutanea tarda (PCT) usually is not passed down in families. In PCT, certain triggers can cause a buildup of porphyrins that may cause symptoms. Examples of triggers include: Too much iron in the body, often due to a condition called hemochromatosis, which is caused by a gene change. Viral infections, such as HIV or hepatitis C. Heavy alcohol use. Smoking. Hormones changes during the menstrual period. […] In addition to genetic risk factors, environmental risk factors may trigger symptoms in porphyria. When exposed to the trigger, the body’s demand for heme production increases. This overwhelms the low level of a needed enzyme, setting in motion a process that causes a buildup of porphyrins.

• #48 Porphyria Overview: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1389981-overview

  The mutations that underlie porphyria result in accumulation and increased excretion of porphyrins and their precursors. Clinical manifestations depend on the step in the heme production pathway in which the enzymatic defect occurs. […] In both type I and type II PCT, clinical expression most often follows exposure to environmental hepatotoxins, such as polyhalogenated aromatic hydrocarbons or ethanol, or to infectious agents such as hepatitis C virus (HCV). […] Hepatoerythropoietic porphyria is a rare autosomal recessive disease that results from severely deficient UROD activity due to the mutation of both UROD alleles (homozygosity or compound heterozygosity). […] In porphyria cutanea tarda (PCT) and hepatoerythropoietic porphyria (HEP), the enzyme uroporphyrinogen decarboxylase is deficient and it leads to a buildup of porphyrias and precursors that spill out of the liver and accumulate in other parts of the body, such as skin, urine, and stool.

• #49 Porphyria – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/porphyria/symptoms-causes/syc-20356066

  Just because you inherit a gene or genes that can cause porphyria doesn’t mean that you’ll have symptoms. You might never have symptoms. This also is the case for most carriers of the changed genes. […] Porphyria cutanea tarda (PCT) usually is not passed down in families. In PCT, certain triggers can cause a buildup of porphyrins that may cause symptoms. Examples of triggers include: Too much iron in the body, often due to a condition called hemochromatosis, which is caused by a gene change. Viral infections, such as HIV or hepatitis C. Heavy alcohol use. Smoking. Hormones changes during the menstrual period. […] In addition to genetic risk factors, environmental risk factors may trigger symptoms in porphyria. When exposed to the trigger, the body’s demand for heme production increases. This overwhelms the low level of a needed enzyme, setting in motion a process that causes a buildup of porphyrins.

• #50 Acute Porphyrias – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/the-porphyrias/acute-porphyrias

  Acute porphyrias result from deficiency of certain enzymes in the heme biosynthetic pathway, resulting in accumulation of heme precursors that cause intermittent attacks of abdominal pain and neurologic symptoms. […] Many precipitating factors exist, typically accelerating biosynthesis of heme precursors above the catalytic capacity of the defective enzyme. Accumulation of the porphyrin precursors porphobilinogen (PBG) and delta-aminolevulinic acid (ALA), or in the case of ALAD-deficiency porphyria, ALA alone, results. […] Hormonal factors are important. Women are more prone to attacks than men, particularly during periods of hormonal change (eg, during the luteal phase of the menstrual cycle, during oral contraceptive use, during the early weeks of gestation, in the immediate postpartum period).

• #51 Acute porphyria | International Porphyria Network

  https://new.porphyrianet.org/en/content/acute-porphyria

  Acute porphyria is caused by a change to a particle of DNA known as a gene; a different gene is affected in each of the different types of acute porphyria. […] Most people who inherit acute porphyria will never experience an acute attack. […] In those who do become ill, additional factors are usually required for an attack to occur. […] Our knowledge of these factors/triggers is incomplete but among the most important are a number of medicines, alcohol, stress, fasting or restricting calorie intake, infections and smoking. […] Women are about five times more likely than men to experience an acute attack, due mostly to female hormones, particularly progesterone. […] The risk of an affected person passing this variant gene on to any of his or her children is one chance in two (50%).

• #52 Acute Hepatic Porphyria: Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/24112-acute-hepatic-porphyria

  Acute hepatic porphyria (AHP) is a group of rare genetic disorders that begin in your liver and go on to affect your nervous system, causing symptoms throughout your body. […] Porphyria is a deficiency in one of the enzymes that your body needs to make heme (a component of hemoglobin in your blood). During the process of making heme, the absence of specific enzymes causes other compounds to go unused and build up in your body tissues. These leftover compounds called porphyrin precursors are toxic when they build up. In acute hepatic porphyria, they build up in your liver first. […] Genetic mutations are the original cause of AHP, but having the gene mutation isn’t usually enough to trigger the onset of symptoms. Most commonly, hormone changes in puberty trigger them for the first time. Other factors that can trigger them are prescription and recreational drug use, excessive alcohol use, severe calorie restriction and illnesses that cause significant stress to your metabolic system.

• #53 Acute porphyria | International Porphyria Network

  https://new.porphyrianet.org/en/content/acute-porphyria

  Acute porphyria is caused by a change to a particle of DNA known as a gene; a different gene is affected in each of the different types of acute porphyria. […] Most people who inherit acute porphyria will never experience an acute attack. […] In those who do become ill, additional factors are usually required for an attack to occur. […] Our knowledge of these factors/triggers is incomplete but among the most important are a number of medicines, alcohol, stress, fasting or restricting calorie intake, infections and smoking. […] Women are about five times more likely than men to experience an acute attack, due mostly to female hormones, particularly progesterone. […] The risk of an affected person passing this variant gene on to any of his or her children is one chance in two (50%).

• #54 Acute Porphyrias – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/the-porphyrias/acute-porphyrias

  Acute porphyrias result from deficiency of certain enzymes in the heme biosynthetic pathway, resulting in accumulation of heme precursors that cause intermittent attacks of abdominal pain and neurologic symptoms. […] Many precipitating factors exist, typically accelerating biosynthesis of heme precursors above the catalytic capacity of the defective enzyme. Accumulation of the porphyrin precursors porphobilinogen (PBG) and delta-aminolevulinic acid (ALA), or in the case of ALAD-deficiency porphyria, ALA alone, results. […] Hormonal factors are important. Women are more prone to attacks than men, particularly during periods of hormonal change (eg, during the luteal phase of the menstrual cycle, during oral contraceptive use, during the early weeks of gestation, in the immediate postpartum period).

• #55 Skin Disease in Porphyria | Porphyria for Patients

  https://porphyria.uct.ac.za/porphyria-patients/about-porphyria/skin-disease-porphyria

  Skin disease is limited to: […] There is a reason for this. It is the porphyrins which interact with sunlight to cause damage as described below. […] In patients with porphyria, high levels of porphyrins may circulate in the blood and are deposited in the skin. Porphyrins are photoactive molecules, the property responsible for their fluorescence. […] It is for this reason that the skin disease of porphyria is usually restricted to areas which are exposed to the sun, and that avoiding sun exposure is so important in preventing skin disease.

• #56 Acute porphyria | International Porphyria Network

  https://new.porphyrianet.org/en/content/acute-porphyria

  Acute porphyria is caused by a change to a particle of DNA known as a gene; a different gene is affected in each of the different types of acute porphyria. […] Most people who inherit acute porphyria will never experience an acute attack. […] In those who do become ill, additional factors are usually required for an attack to occur. […] Our knowledge of these factors/triggers is incomplete but among the most important are a number of medicines, alcohol, stress, fasting or restricting calorie intake, infections and smoking. […] Women are about five times more likely than men to experience an acute attack, due mostly to female hormones, particularly progesterone. […] The risk of an affected person passing this variant gene on to any of his or her children is one chance in two (50%).

• #57 Acute Intermittent Porphyria: Diagnosis and Treatment

  https://www.healthline.com/health/hl-clinical-growth-diagnosing-and-treating-acute-intermittent-porphyria

  A mutation that impacts an enzyme involved in heme biosynthesis causes porphyrias, which are inheritable metabolic disorders. […] An HMBS gene mutation causes the disorder. […] Doctors diagnose AIP 1.5 to 2 times more often in women than men. Experts think that hormones associated with the menstrual cycle cause this. […] Outside factors, like medications, alcohol, hormonal changes, or insufficient calorie intake, typically trigger episodes of AIP when symptoms occur. […] Some medications can be triggers for AIP if someone has a genetic mutation for it. […] The only cure currently available for AIP is an orthotopic liver transplant. […] AIP is an inheritable condition associated with enzymes affecting the heme biosynthesis pathway.

• #58 Porphyria – NIDDK

  https://www.niddk.nih.gov/health-information/liver-disease/porphyria

  Porphyrias are rare disorders that mainly affect the skin or nervous system. These disorders are usually inherited, meaning they are caused by gene mutations passed from parents to children. […] Most types of porphyrias are caused by gene mutations. Some types of porphyrias result from inheriting a gene mutation from one parent, while other types result from inheriting two gene mutations, one from each parent. […] The most common type of porphyria, porphyria cutanea tarda, is most often acquired, meaning that factors other than inherited genes may cause this condition. These factors may include a buildup of iron in the body, which may be caused by gene mutations that can lead to hemochromatosis.

• #59 Porphyria cutanea tarda: Causes, symptoms, and diagnosis

  https://www.medicalnewstoday.com/articles/318543

  Porphyria cutanea tarda (PCT) is the most common form of porphyria but is still rare, affecting only 1 in every 10,000 to 25,000 people in the general population. […] PCT is a cutaneous porphyria caused by a deficiency of the enzyme uroporphyrinogen decarboxylase (UROD), which helps convert porphyrins into heme. […] PCT occurs when the body’s ability to make UROD is interrupted. […] PCT can be caused by hepatitis C, HIV, and excessive alcohol consumption. […] A minority of people with the condition have familial PCT, which means the UROD deficiency is genetic.

• #60 Porphyria Overview: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1389981-overview

  Porphyria is the common term for a group of syndromes, largely hereditary, that result from defects in porphyrins (the enzymes involved in heme synthesis). Depending on the specific enzyme affected, porphyria may manifest clinically in an acute or non-acute manner, and the signs and symptoms may be predominantly neurovisceral, psychiatric, cutaneous, or some combination of those. […] Porphyrias can be inherited or (rarely) acquired. There are at least 8 different types of porphyrias. Acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), variegate porphyria (VP), and the familial form of porphyria cutanea tarda (PCT) follow an autosomal dominant inheritance pattern with low penetration. Aminolevulinic acid dehydratase deficiency porphyria (ADP), congenital erythropoietic porphyria (CEP), erythropoietic protoporphyria (EPP), and hepatoerythropoietic porphyria (HEP) are autosomal recessive. There is also an X-linked dominant inherited porphyria called X-linked protoporphyria (XLP).

• #61 Porphyria Cutanea Tarda: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1103643-overview

  Porphyria cutanea tarda (PCT), the most common type of porphyria, is a metabolic disorder in which activity of the heme synthetic enzyme uroporphyrinogen decarboxylase (UROD) is deficient. […] Two types of PCT are recognized: sporadic (acquired) type I PCT and autodomal dominant (hereditary) type II PCT. Approximately 80% of all cases of PCT are acquired and 20% familial, though the ratio may vary in different geographic regions and ethnic groups. […] Familial PCT most often arises from autosomal dominant inheritance of a single mutation of the gene UROD. […] The common acquired form, sporadic PCT, occurs in individuals whose UROD DNA sequences are normal but who may have other genetically determined susceptibilities to inhibition of UROD activity. Ethanol intake, estrogen therapy, hemochromatosis, hepatitis C, and HIV infection are the major predisposing factors.

• #62 Porphyria Cutanea Tarda: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1103643-overview

  Porphyria cutanea tarda (PCT), the most common type of porphyria, is a metabolic disorder in which activity of the heme synthetic enzyme uroporphyrinogen decarboxylase (UROD) is deficient. […] Two types of PCT are recognized: sporadic (acquired) type I PCT and autodomal dominant (hereditary) type II PCT. Approximately 80% of all cases of PCT are acquired and 20% familial, though the ratio may vary in different geographic regions and ethnic groups. […] Familial PCT most often arises from autosomal dominant inheritance of a single mutation of the gene UROD. […] The common acquired form, sporadic PCT, occurs in individuals whose UROD DNA sequences are normal but who may have other genetically determined susceptibilities to inhibition of UROD activity. Ethanol intake, estrogen therapy, hemochromatosis, hepatitis C, and HIV infection are the major predisposing factors.

• #63 Porphyria Cutanea Tarda: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1103643-overview

  Clinical expression of both sporadic and familial PCT most often requires exposure to environmental or infectious agents or the presence of coexisting conditions that adversely affect hepatocytes and result in hepatic siderosis. […] The unifying underlying cause of all forms of PCT is reduction of UROD activity to a critical point during hepatic heme synthesis. Genetic, environmental, or infectious contributory or susceptibility factors, acting singly or (more often) in concert, inhibit UROD activity to that critical point of insufficiency, resulting in the onset of clinical symptoms. […] Alcohol effects on hepatocytes may precipitate PCT by making stored hepatic iron more available for catalyzing oxidation reactions, by generating reactive oxygen species (ROS), or by inducing hepatic cytochromes, all of which may facilitate oxidation of uroporphyrinogen to UROD inhibitors.

• #64 Porphyria Cutanea Tarda: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1103643-overview

  Porphyria cutanea tarda (PCT), the most common type of porphyria, is a metabolic disorder in which activity of the heme synthetic enzyme uroporphyrinogen decarboxylase (UROD) is deficient. […] Two types of PCT are recognized: sporadic (acquired) type I PCT and autodomal dominant (hereditary) type II PCT. Approximately 80% of all cases of PCT are acquired and 20% familial, though the ratio may vary in different geographic regions and ethnic groups. […] Familial PCT most often arises from autosomal dominant inheritance of a single mutation of the gene UROD. […] The common acquired form, sporadic PCT, occurs in individuals whose UROD DNA sequences are normal but who may have other genetically determined susceptibilities to inhibition of UROD activity. Ethanol intake, estrogen therapy, hemochromatosis, hepatitis C, and HIV infection are the major predisposing factors.

• #65 Porphyria – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/porphyria/symptoms-causes/syc-20356066

  Just because you inherit a gene or genes that can cause porphyria doesn’t mean that you’ll have symptoms. You might never have symptoms. This also is the case for most carriers of the changed genes. […] Porphyria cutanea tarda (PCT) usually is not passed down in families. In PCT, certain triggers can cause a buildup of porphyrins that may cause symptoms. Examples of triggers include: Too much iron in the body, often due to a condition called hemochromatosis, which is caused by a gene change. Viral infections, such as HIV or hepatitis C. Heavy alcohol use. Smoking. Hormones changes during the menstrual period. […] In addition to genetic risk factors, environmental risk factors may trigger symptoms in porphyria. When exposed to the trigger, the body’s demand for heme production increases. This overwhelms the low level of a needed enzyme, setting in motion a process that causes a buildup of porphyrins.

• #66 Porphyria – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/porphyria/symptoms-causes/syc-20356066

  Just because you inherit a gene or genes that can cause porphyria doesn’t mean that you’ll have symptoms. You might never have symptoms. This also is the case for most carriers of the changed genes. […] Porphyria cutanea tarda (PCT) usually is not passed down in families. In PCT, certain triggers can cause a buildup of porphyrins that may cause symptoms. Examples of triggers include: Too much iron in the body, often due to a condition called hemochromatosis, which is caused by a gene change. Viral infections, such as HIV or hepatitis C. Heavy alcohol use. Smoking. Hormones changes during the menstrual period. […] In addition to genetic risk factors, environmental risk factors may trigger symptoms in porphyria. When exposed to the trigger, the body’s demand for heme production increases. This overwhelms the low level of a needed enzyme, setting in motion a process that causes a buildup of porphyrins.

• #67 Porphyria: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/porphyria/

  Porphyria is a group of disorders caused by abnormalities in the chemical steps that lead to heme production. […] Researchers have identified several types of porphyria, which are distinguished by their genetic cause and their signs and symptoms. […] Each form of porphyria results from mutations in one of these genes: ALAD, ALAS2, CPOX, FECH, HMBS, PPOX, UROD, or UROS. […] The genes related to porphyria provide instructions for making the enzymes needed to produce heme. Mutations in most of these genes reduce enzyme activity, which limits the amount of heme the body can produce. […] One type of porphyria, porphyria cutanea tarda, results from both genetic and nongenetic factors. […] Many factors contribute to the development of porphyria cutanea tarda. These include an increased amount of iron in the liver, alcohol consumption, smoking, hepatitis C or HIV infection, or certain hormones. […] Mutations in the HFE gene (which cause an iron overload disorder called hemochromatosis) are also associated with porphyria cutanea tarda. […] Other, as-yet-unidentified genetic factors may also play a role in this form of porphyria.

• #68 Porphyria Cutanea Tarda: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1103643-overview

  Clinical expression of both sporadic and familial PCT most often requires exposure to environmental or infectious agents or the presence of coexisting conditions that adversely affect hepatocytes and result in hepatic siderosis. […] The unifying underlying cause of all forms of PCT is reduction of UROD activity to a critical point during hepatic heme synthesis. Genetic, environmental, or infectious contributory or susceptibility factors, acting singly or (more often) in concert, inhibit UROD activity to that critical point of insufficiency, resulting in the onset of clinical symptoms. […] Alcohol effects on hepatocytes may precipitate PCT by making stored hepatic iron more available for catalyzing oxidation reactions, by generating reactive oxygen species (ROS), or by inducing hepatic cytochromes, all of which may facilitate oxidation of uroporphyrinogen to UROD inhibitors.

• #69 Porphyria Cutanea Tarda: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1103643-overview

  A strong association between PCT and hereditary hemochromatosis genes causing hepatic siderosis has been established. […] Hepatitis virus infections are frequently associated with PCT. […] Tobacco smoking is a behavioral characteristic frequently observed among patients with PCT. […] Environmental exposure to aromatic polyhalogenated hepatotoxins also induces hepatic cytochromes, thus potentiating production of oxidation products capable of inhibiting UROD activity.

• #70 Porphyria | UCSF Department of Surgery

  https://surgery.ucsf.edu/condition/porphyria

  Porphyrias are rare disorders that affect mainly the skin or nervous system and may cause abdominal pain. These disorders are usually inherited, meaning they are caused by abnormalities in genes passed from parents to children. […] Most porphyrias are inherited disorders. Scientists have identified genes for all eight enzymes in the heme biosynthetic pathway. Most porphyrias result from inheriting an abnormal gene, also called a gene mutation, from one parent. Some porphyrias, such as congenital erythropoietic porphyria, hepatoerythropoietic porphyria, and erythropoietic protoporphyria, occur when a person inherits two abnormal genes, one from each parent. The likeliness of a person passing the abnormal gene or genes to the next generation depends on the type of porphyria. […] Porphyria cutanea tarda is usually an acquired disorder, meaning factors other than genes cause the enzyme deficiency. This type of porphyria can be triggered by too much iron, use of alcohol or estrogen, smoking, chronic hepatitis, HIV, and abnormal genes associated with hemochromatosis.

• #71 Porphyria Cutanea Tarda: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1103643-overview

  Porphyria cutanea tarda (PCT), the most common type of porphyria, is a metabolic disorder in which activity of the heme synthetic enzyme uroporphyrinogen decarboxylase (UROD) is deficient. […] Two types of PCT are recognized: sporadic (acquired) type I PCT and autodomal dominant (hereditary) type II PCT. Approximately 80% of all cases of PCT are acquired and 20% familial, though the ratio may vary in different geographic regions and ethnic groups. […] Familial PCT most often arises from autosomal dominant inheritance of a single mutation of the gene UROD. […] The common acquired form, sporadic PCT, occurs in individuals whose UROD DNA sequences are normal but who may have other genetically determined susceptibilities to inhibition of UROD activity. Ethanol intake, estrogen therapy, hemochromatosis, hepatitis C, and HIV infection are the major predisposing factors.

• #72 Porphyria Cutanea Tarda: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1103643-overview

  A strong association between PCT and hereditary hemochromatosis genes causing hepatic siderosis has been established. […] Hepatitis virus infections are frequently associated with PCT. […] Tobacco smoking is a behavioral characteristic frequently observed among patients with PCT. […] Environmental exposure to aromatic polyhalogenated hepatotoxins also induces hepatic cytochromes, thus potentiating production of oxidation products capable of inhibiting UROD activity.

• #73 Porphyria Cutanea Tarda: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1103643-overview

  A strong association between PCT and hereditary hemochromatosis genes causing hepatic siderosis has been established. […] Hepatitis virus infections are frequently associated with PCT. […] Tobacco smoking is a behavioral characteristic frequently observed among patients with PCT. […] Environmental exposure to aromatic polyhalogenated hepatotoxins also induces hepatic cytochromes, thus potentiating production of oxidation products capable of inhibiting UROD activity.

• #74 Acute Porphyria – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK537352/

  Acute porphyrias are genetic conditions; however, environmental, e.g., drugs and physiological factors, are crucial for clinical manifestation. […] Porphyria is a genetic disorder. […] More than 100 mutations have been identified. […] Clinical manifestation is associated with a 50% or more reduction in enzyme function. […] Hereditary coproporphyria is caused by significant heterogeneity and abnormal functioning of coproporphyrinogen oxidase. […] A 50% reduction in protoporphyrinogen oxidase is present in all the samples tested. […] The pathogenesis of neurovisceral symptoms in acute porphyria has not been fully elucidated. […] The enzyme affected is porphobilinogen (PBG) deaminase also referred to as Hydroxymethylbilane synthase (HMBS). […] The rarest acute porphyria, which is caused by a defect in the enzyme ALA dehydratase, is known as delta-aminolevulinic aciduria or ALA dehydratase deficiency (ALAD) and has an autosomal recessive inheritance pattern.

• #75 Acute Intermittent Porphyria (AIP) – American Porphyria Foundation

  https://porphyriafoundation.org/for-patients/types-of-porphyria/aip/

  The exact, underlying reasons why symptoms only develop in some individuals with the genetic mutation for AIP are not fully understood. […] One theory states that a specific porphyrin precursor (most likely ALA) is a hepatic (liver) neurotoxin that damages nerve tissue. […] A second theory suggests that heme deficiency in nerve cells (neurons) contributes to the development of symptoms.

• #76 Acute Intermittent Porphyria (AIP) – American Porphyria Foundation

  https://porphyriafoundation.org/for-patients/types-of-porphyria/aip/

  The exact, underlying reasons why symptoms only develop in some individuals with the genetic mutation for AIP are not fully understood. […] One theory states that a specific porphyrin precursor (most likely ALA) is a hepatic (liver) neurotoxin that damages nerve tissue. […] A second theory suggests that heme deficiency in nerve cells (neurons) contributes to the development of symptoms.

• #77 Porphyria | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/porphyria-1?lang=us

  Porphyrias are a group of rare metabolic diseases in which heme metabolism is altered. […] Acute intermittent porphyria has a prevalence of 1 in 1600 Caucasians but a low clinical penetrance of approximately 2-3%. […] Porphyrin can be overproduced in the liver or bone marrow, therefore some authors classify porphyrias as erythropoietic or hepatic according to the main site of overproduction of heme precursors. […] The pathophysiology of acute attacks is complex and varies depending on subtype. It is postulated that raised concentrations of aminolevulinic acid and porphobilinogen cause neurotoxicity either directly, by interacting with receptors structurally similar to gamma-aminobutyric acid, or by forming free radicals and reactive oxygen species. […] Patients should be counseled on avoidance of triggers and monitored for long term complications including hepatocellular carcinoma.

• #78 Acute Intermittent Porphyria (AIP) – American Porphyria Foundation

  https://porphyriafoundation.org/for-patients/types-of-porphyria/aip/

  The exact, underlying reasons why symptoms only develop in some individuals with the genetic mutation for AIP are not fully understood. […] One theory states that a specific porphyrin precursor (most likely ALA) is a hepatic (liver) neurotoxin that damages nerve tissue. […] A second theory suggests that heme deficiency in nerve cells (neurons) contributes to the development of symptoms.

• #79 Acute Porphyrias – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/the-porphyrias/acute-porphyrias

  Acute porphyrias result from deficiency of certain enzymes in the heme biosynthetic pathway, resulting in accumulation of heme precursors that cause intermittent attacks of abdominal pain and neurologic symptoms. […] Many precipitating factors exist, typically accelerating biosynthesis of heme precursors above the catalytic capacity of the defective enzyme. Accumulation of the porphyrin precursors porphobilinogen (PBG) and delta-aminolevulinic acid (ALA), or in the case of ALAD-deficiency porphyria, ALA alone, results. […] Hormonal factors are important. Women are more prone to attacks than men, particularly during periods of hormonal change (eg, during the luteal phase of the menstrual cycle, during oral contraceptive use, during the early weeks of gestation, in the immediate postpartum period).

• #80 Acute Porphyrias – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/the-porphyrias/acute-porphyrias

  Acute porphyrias result from deficiency of certain enzymes in the heme biosynthetic pathway, resulting in accumulation of heme precursors that cause intermittent attacks of abdominal pain and neurologic symptoms. […] Many precipitating factors exist, typically accelerating biosynthesis of heme precursors above the catalytic capacity of the defective enzyme. Accumulation of the porphyrin precursors porphobilinogen (PBG) and delta-aminolevulinic acid (ALA), or in the case of ALAD-deficiency porphyria, ALA alone, results. […] Hormonal factors are important. Women are more prone to attacks than men, particularly during periods of hormonal change (eg, during the luteal phase of the menstrual cycle, during oral contraceptive use, during the early weeks of gestation, in the immediate postpartum period).

• #81 Acute Hepatic Porphyria: Causes, Symptoms & Treatments

  https://liverfoundation.org/liver-diseases/rare-disease/acute-hepatic-porphyria-ahp/

  Porphyria refers to a group of diseases that affect fewer than 200,000 people. Acute Hepatic Porphyria (AHP) refers to a family of rare genetic diseases characterized by potentially life-threatening attacks and, for some people, chronic (ongoing and sometimes lifelong) pain and other symptoms that interfere in their ability to live normal lives. […] AHP is a hereditary disease, meaning that it can be passed from parents to children. This can occur if either one or both parents carry the defective gene, depending on the AHP type. […] AHP occurs when there is a problem with heme production in the liver. When heme is not produced properly, certain toxins called PBG (porphobilinogen) and ALA (aminolevulinic acid) accumulate in the liver and can further circulate throughout the body. ALA and PBG are associated with the painful attacks and other disease manifestations people with AHP experience. […] There is no cure for AHP, but there are ways to manage its symptoms. The U.S. Food and Drug Administration has approved some medications that doctors may prescribe to either reduce or treat AHP attacks.

• #82 Porphyria Urine: Color, Giving a Sample, What It Means

  https://www.verywellhealth.com/porphyria-urine-color-giving-a-sample-what-it-means-5207798

  Porphyria is a group of disorders caused by abnormal function of the enzymes involved in the production of heme. […] The production of heme in the bone marrow and liver will normally create a certain amount of porphyrins, but if the heme-producing enzymes are out of balance, porphyrins can build up and become toxic. […] Porphyrias usually develop because of an inherited genetic mutation. The mutation causes problems with the enzymes that work together to create blood cells. […] There are also rare forms of porphyria that are not caused by genetic mutations. These conditions are called acquired porphyrias. Possible causes of acquired porphyria include: Lead exposure, HIV (human immunodeficiency virus), Hepatitis C, Excessive iron intake, Alcohol use disorders.

• #83 Porphyrias – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/porphyrias/

  Porphyrias are a group of rare, inherited or (less commonly) acquired metabolic disorders in which defective enzymes impair the biosynthesis of heme in the liver and/or bone marrow. […] An important acquired form of porphyria is lead poisoning, which is discussed in another article (see Metal toxicity). […] Etiology and pathophysiology [2][3] […] Reduced activity of heme biosynthesis enzyme uroporphyrinogen III decarboxylase (UROD) uroporphyrin accumulates in the skin sunlight-dependent skin damage (chronic photosensitivity) […] Type I: acquired (sporadic) deficiency of UROD […] Type II: inherited/familial (autosomal dominant) UROD mutation. […] Susceptibility factors […] Iron overload leading to increased hepatic iron stores (PCT is an iron-related disease) […] Primary (genetic): hemochromatosis

• #84 Porphyrias – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/porphyrias/

  Porphyrias are a group of rare, inherited or (less commonly) acquired metabolic disorders in which defective enzymes impair the biosynthesis of heme in the liver and/or bone marrow. […] An important acquired form of porphyria is lead poisoning, which is discussed in another article (see Metal toxicity). […] Etiology and pathophysiology [2][3] […] Reduced activity of heme biosynthesis enzyme uroporphyrinogen III decarboxylase (UROD) uroporphyrin accumulates in the skin sunlight-dependent skin damage (chronic photosensitivity) […] Type I: acquired (sporadic) deficiency of UROD […] Type II: inherited/familial (autosomal dominant) UROD mutation. […] Susceptibility factors […] Iron overload leading to increased hepatic iron stores (PCT is an iron-related disease) […] Primary (genetic): hemochromatosis

• #85 Porphyria Urine: Color, Giving a Sample, What It Means

  https://www.verywellhealth.com/porphyria-urine-color-giving-a-sample-what-it-means-5207798

  Porphyria is a group of disorders caused by abnormal function of the enzymes involved in the production of heme. […] The production of heme in the bone marrow and liver will normally create a certain amount of porphyrins, but if the heme-producing enzymes are out of balance, porphyrins can build up and become toxic. […] Porphyrias usually develop because of an inherited genetic mutation. The mutation causes problems with the enzymes that work together to create blood cells. […] There are also rare forms of porphyria that are not caused by genetic mutations. These conditions are called acquired porphyrias. Possible causes of acquired porphyria include: Lead exposure, HIV (human immunodeficiency virus), Hepatitis C, Excessive iron intake, Alcohol use disorders.

• #86 Porphyria – Wikipedia

  https://en.wikipedia.org/wiki/Porphyria

  Most types of porphyria are inherited from one or both of a person’s parents and are due to a mutation in one of the genes that make heme. […] The underlying mechanism results in a decrease in the amount of heme produced and a build-up of substances involved in making heme. […] The porphyrias are generally considered genetic in nature. […] Subtypes of porphyrias depend on which enzyme is deficient. […] In the autosomal recessive types, anyone who inherit a single gene may become a carrier. Generally they do not have symptoms but may pass the gene on to offspring. […] Some liver diseases may cause porphyria even in the absence of genetic predisposition. These include hemochromatosis and hepatitis C.

• #87 Porphyrias | Choose the Right Test

  https://arupconsult.com/content/porphyrias

  The porphyrias are caused by loss (or gain, in the case of X-linked erythropoietic protoporphyria [XLP]) of specific enzyme functions in the heme biosynthesis pathway. […] Initial testing includes porphobilinogen (PBG) measurement, urine porphyrin fractionation, and erythrocyte protoporphyrin measurements. […] Genetic testing can provide definitive diagnosis but is usually not required. […] Patients with acute hepatic porphyrias are at greater risk for hepatic fibrosis or cirrhosis, as well as hepatocellular carcinoma (HCC). […] Pseudoporphyria is a photodistributed bullous disorder. […] Diagnostic testing for porphyrias should be performed in individuals who present with severe, diffuse neuropathic abdominal pain and accompanying symptoms and in individuals with cutaneous photosensitivity.

• #88 Acute Porphyrias – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/the-porphyrias/acute-porphyrias

  Treatment of the acute attack is identical for all acute porphyrias. Possible triggers (eg, excessive alcohol use, medications) are identified and eliminated. […] Givosiran can be used to treat adults with acute hepatic porphyria to prevent recurrent acute attacks. […] Liver transplantation remains an option. Successful liver transplantation leads to permanent cure of acute intermittent porphyria. […] The incidence of hepatocellular cancer is high among carriers of acute porphyria, especially in patients with active disease.

• #89 Acute Porphyria – MD Searchlight

  https://mdsearchlight.com/genetic-disorders/acute-porphyria/

  In all the tests conducted, a 50% reduction in an enzyme called protoporphyrinogen oxidase was found. […] There have been findings suggesting a link between acute porphyria and liver cancer, particularly in the case of Acute Intermittent Porphyria (AIP). […] AIP also has been found to increase the risk of high blood pressure and chronic kidney disease. […] Chronic pain is another problem associated with repeated attacks of acute porphyria.

• #90 Acute Porphyrias – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/the-porphyrias/acute-porphyrias

  Other factors include medications, particularly those that induce hepatic ALA synthase-1 and cytochrome P-450 enzymes. […] A minority of patients with acute hepatic porphyrias also develop acute pancreatitis, for which alternative potential causes, such as gallstones, excess alcohol use, and severe hypertriglyceridemia, are not found. […] Chronic kidney disease in acute porphyria is multifactorial; acute hypertension (possibly leading to chronic hypertension) is likely a main precipitating factor. However, genetic factors, especially a genetic variation in the peptide transporter 2 (PEPT2) gene, which encodes a peptide and amino acid transporter that can affect reabsorption of ALA in the proximal tubule, have been found in patients with acute intermittent porphyria who have developed chronic kidney disease.

• #91 Acute Porphyria – MD Searchlight

  https://mdsearchlight.com/genetic-disorders/acute-porphyria/

  In all the tests conducted, a 50% reduction in an enzyme called protoporphyrinogen oxidase was found. […] There have been findings suggesting a link between acute porphyria and liver cancer, particularly in the case of Acute Intermittent Porphyria (AIP). […] AIP also has been found to increase the risk of high blood pressure and chronic kidney disease. […] Chronic pain is another problem associated with repeated attacks of acute porphyria.

• #92 Porphyria: Treatment, Procedure, Cost, Recovery, Side Effects And More

  https://www.lybrate.com/topic/porphyria

  Long-term side effects or complications of porphyria include problems with the nervous system and mental health conditions. […] Porphyria is a condition in which the body is unable to properly process hemoglobin, which is a major component of blood. This is a rare, serious, and potentially life-threatening condition that can cause harm to the liver and nervous system. […] Porphyria is an acute or chronic condition caused by a lack of heme pigment in the blood and liver. The acute variety is caused by exposure to sunlight or certain drugs, while the chronic variety has non-acute symptoms and is inherited.

• #93 Porphyria

  https://www.pediatriconcall.com/articles/genetics/porphyria/porphyria-introduction

  Most of the patients who inherit the disorder enjoy normal health, However, they are at risk of developing an attack if exposed to various precipitating factors such as alcohol, infection, dieting, and drugs. […] The drugs commonly causing the acute attack are: Diuretics like frusemide, hydrochlorothiazide […] Antihypertensives like Alpha Methyl Dopa, Enalapril, Hydralazine, Lisinopril, Nifedipine, Verapamil […] Antihistamines like Dimenhydrinate, Terfenadine. […] Hypnotics like Amylobarbitone, Diazepam, Flurazepam. […] Anticonvulsants like Barbiturates, carbamazepine, ethosuximide, Hydantoins, Phenytoin. […] Antibiotics: Chloramphenicol, Erythromycin, Cloxacillin, Griseofulvin, Pyrazinamide, Sulphonamides. […] Miscellaneous-Oral contraceptives, Sulphonylureas, Ergotamine. […] Skin problems in porphyria are usually acquired conditions. Patients with VP, HC, CP, and PCT have very sensitive skin, which is easily damaged. […] Long term, their skin becomes thin, dark, scarred, and often hairy. […] There is no cure for porphyria. However, it can be made less severe. Patients with PCT should avoid alcohol.

• #94 Acute Porphyrias – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/the-porphyrias/acute-porphyrias

  Treatment of the acute attack is identical for all acute porphyrias. Possible triggers (eg, excessive alcohol use, medications) are identified and eliminated. […] Givosiran can be used to treat adults with acute hepatic porphyria to prevent recurrent acute attacks. […] Liver transplantation remains an option. Successful liver transplantation leads to permanent cure of acute intermittent porphyria. […] The incidence of hepatocellular cancer is high among carriers of acute porphyria, especially in patients with active disease.

• #95 Hepatic Porphyria | Conditions | UCSF Health

  https://www.ucsfhealth.org/conditions/hepatic-porphyria

  Treatment for hepatic porphyria focuses on avoiding triggers such as alcohol consumption or too much iron in the body that lead to symptoms. […] Treatment for hepatic porphyria depends on the type. However, for both cutaneous and acute porphyria, the first step of therapy involves identifying and eliminating the precipitating factors, such as alcohol, certain medication or excess iron. […] For patients with cutaneous porphyria whose iron levels are high, iron depletion is recommended. […] The best form of treatment for acute porphyria is prevention. […] When acute porphyria progresses despite elimination of triggering factors, hospitalization is necessary. Specific treatment involves administration of intravenous hematin, which compensates for the genetic deficiency.

• #96 Hepatic Porphyria | Conditions | UCSF Health

  https://www.ucsfhealth.org/conditions/hepatic-porphyria

  Treatment for hepatic porphyria focuses on avoiding triggers such as alcohol consumption or too much iron in the body that lead to symptoms. […] Treatment for hepatic porphyria depends on the type. However, for both cutaneous and acute porphyria, the first step of therapy involves identifying and eliminating the precipitating factors, such as alcohol, certain medication or excess iron. […] For patients with cutaneous porphyria whose iron levels are high, iron depletion is recommended. […] The best form of treatment for acute porphyria is prevention. […] When acute porphyria progresses despite elimination of triggering factors, hospitalization is necessary. Specific treatment involves administration of intravenous hematin, which compensates for the genetic deficiency.

• #97 Acute Porphyrias – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/the-porphyrias/acute-porphyrias

  Treatment of the acute attack is identical for all acute porphyrias. Possible triggers (eg, excessive alcohol use, medications) are identified and eliminated. […] Givosiran can be used to treat adults with acute hepatic porphyria to prevent recurrent acute attacks. […] Liver transplantation remains an option. Successful liver transplantation leads to permanent cure of acute intermittent porphyria. […] The incidence of hepatocellular cancer is high among carriers of acute porphyria, especially in patients with active disease.

• #98 Acute Hepatic Porphyria: Causes, Symptoms & Treatments

  https://liverfoundation.org/liver-diseases/rare-disease/acute-hepatic-porphyria-ahp/

  Porphyria refers to a group of diseases that affect fewer than 200,000 people. Acute Hepatic Porphyria (AHP) refers to a family of rare genetic diseases characterized by potentially life-threatening attacks and, for some people, chronic (ongoing and sometimes lifelong) pain and other symptoms that interfere in their ability to live normal lives. […] AHP is a hereditary disease, meaning that it can be passed from parents to children. This can occur if either one or both parents carry the defective gene, depending on the AHP type. […] AHP occurs when there is a problem with heme production in the liver. When heme is not produced properly, certain toxins called PBG (porphobilinogen) and ALA (aminolevulinic acid) accumulate in the liver and can further circulate throughout the body. ALA and PBG are associated with the painful attacks and other disease manifestations people with AHP experience. […] There is no cure for AHP, but there are ways to manage its symptoms. The U.S. Food and Drug Administration has approved some medications that doctors may prescribe to either reduce or treat AHP attacks.

• #99 Acute Porphyrias – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/the-porphyrias/acute-porphyrias

  Treatment of the acute attack is identical for all acute porphyrias. Possible triggers (eg, excessive alcohol use, medications) are identified and eliminated. […] Givosiran can be used to treat adults with acute hepatic porphyria to prevent recurrent acute attacks. […] Liver transplantation remains an option. Successful liver transplantation leads to permanent cure of acute intermittent porphyria. […] The incidence of hepatocellular cancer is high among carriers of acute porphyria, especially in patients with active disease.

• #100 Acute Porphyrias – Endocrine and Metabolic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/the-porphyrias/acute-porphyrias

  Treatment of the acute attack is identical for all acute porphyrias. Possible triggers (eg, excessive alcohol use, medications) are identified and eliminated. […] Givosiran can be used to treat adults with acute hepatic porphyria to prevent recurrent acute attacks. […] Liver transplantation remains an option. Successful liver transplantation leads to permanent cure of acute intermittent porphyria. […] The incidence of hepatocellular cancer is high among carriers of acute porphyria, especially in patients with active disease.

• #101 Porphyria // Middlesex Health

  https://middlesexhealth.org/learning-center/diseases-and-conditions/porphyria

  In addition to genetic risk factors, environmental risk factors may trigger symptoms in porphyria. When exposed to the trigger, the body’s demand for heme production increases. This overwhelms the low level of a needed enzyme, setting in motion a process that causes a buildup of porphyrins. […] Possible complications depend on the form of porphyria: […] In rare cases, a bone marrow transplant or liver transplant may be needed.

• #102 Porphyria // Middlesex Health

  https://middlesexhealth.org/learning-center/diseases-and-conditions/porphyria

  In addition to genetic risk factors, environmental risk factors may trigger symptoms in porphyria. When exposed to the trigger, the body’s demand for heme production increases. This overwhelms the low level of a needed enzyme, setting in motion a process that causes a buildup of porphyrins. […] Possible complications depend on the form of porphyria: […] In rare cases, a bone marrow transplant or liver transplant may be needed.

• #103 The porphyrias – British Porphyria Association

  http://porphyria.org.uk/the-eight-porphyrias/

  EPP is a less common form of porphyria and classified in the UK as an ultra rare disease. […] It is an inherited disorder that is passed on from parents to their children. […] In EPP, there is a shortage of a particular enzyme (ferrochelatase), which normally helps to convert protoporphyrin into haem by adding iron to it. […] CEP is one of the rarest porphyrias. […] It is a genetic condition that is inherited in a recessive pattern. […] Gene defects cause the enzyme uroporphyrinogen lll cosynthase (UROS) to function ineffectively. […] The most important aspect of day-to-day management of CEP for most patients is the avoidance of sun/light exposure, as well as ultraviolet light and light emitted by fluorescent sources. […] At this time, the only curative treatment option for CEP is Bone Marrow Transplant (BMT) or Hematopoietic Stem Cell Transplant (HSCT).

• #104 Porphyria | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/porphyria-1?lang=us

  Porphyrias are a group of rare metabolic diseases in which heme metabolism is altered. […] Acute intermittent porphyria has a prevalence of 1 in 1600 Caucasians but a low clinical penetrance of approximately 2-3%. […] Porphyrin can be overproduced in the liver or bone marrow, therefore some authors classify porphyrias as erythropoietic or hepatic according to the main site of overproduction of heme precursors. […] The pathophysiology of acute attacks is complex and varies depending on subtype. It is postulated that raised concentrations of aminolevulinic acid and porphobilinogen cause neurotoxicity either directly, by interacting with receptors structurally similar to gamma-aminobutyric acid, or by forming free radicals and reactive oxygen species. […] Patients should be counseled on avoidance of triggers and monitored for long term complications including hepatocellular carcinoma.

• #105 Porphyrias: Overview of classification and evaluation – UpToDate

  https://www.uptodate.com/contents/porphyrias-overview-of-classification-and-evaluation

  Porphyrias are metabolic disorders caused by altered activities of the eight enzymes in the heme biosynthetic pathway. A distinct type of porphyria is associated with each enzyme. […] Although uncommon, porphyrias can be encountered by clinicians in any specialty. Diagnosis is challenging because these diseases are rare and their symptoms nonspecific. […] Porphyrias are readily diagnosed or excluded by appropriate biochemical testing, but this is often problematic due to lack of standardization of tests offered by major referral laboratories. […] This topic provides an overview of the porphyrias, with an emphasis on classification and other information that clinicians in any specialty should know in order to consider porphyria and order appropriate biochemical testing.

• #106 Porphyrias: Overview of classification and evaluation – UpToDate

  https://www.uptodate.com/contents/porphyrias-overview-of-classification-and-evaluation

  Porphyrias are metabolic disorders caused by altered activities of the eight enzymes in the heme biosynthetic pathway. A distinct type of porphyria is associated with each enzyme. […] Although uncommon, porphyrias can be encountered by clinicians in any specialty. Diagnosis is challenging because these diseases are rare and their symptoms nonspecific. […] Porphyrias are readily diagnosed or excluded by appropriate biochemical testing, but this is often problematic due to lack of standardization of tests offered by major referral laboratories. […] This topic provides an overview of the porphyrias, with an emphasis on classification and other information that clinicians in any specialty should know in order to consider porphyria and order appropriate biochemical testing.

• #107 Porphyrias | Choose the Right Test

  https://arupconsult.com/content/porphyrias

  The porphyrias are caused by loss (or gain, in the case of X-linked erythropoietic protoporphyria [XLP]) of specific enzyme functions in the heme biosynthesis pathway. […] Initial testing includes porphobilinogen (PBG) measurement, urine porphyrin fractionation, and erythrocyte protoporphyrin measurements. […] Genetic testing can provide definitive diagnosis but is usually not required. […] Patients with acute hepatic porphyrias are at greater risk for hepatic fibrosis or cirrhosis, as well as hepatocellular carcinoma (HCC). […] Pseudoporphyria is a photodistributed bullous disorder. […] Diagnostic testing for porphyrias should be performed in individuals who present with severe, diffuse neuropathic abdominal pain and accompanying symptoms and in individuals with cutaneous photosensitivity.

• #108 Porphyrias | Choose the Right Test

  https://arupconsult.com/content/porphyrias

  The porphyrias are caused by loss (or gain, in the case of X-linked erythropoietic protoporphyria [XLP]) of specific enzyme functions in the heme biosynthesis pathway. […] Initial testing includes porphobilinogen (PBG) measurement, urine porphyrin fractionation, and erythrocyte protoporphyrin measurements. […] Genetic testing can provide definitive diagnosis but is usually not required. […] Patients with acute hepatic porphyrias are at greater risk for hepatic fibrosis or cirrhosis, as well as hepatocellular carcinoma (HCC). […] Pseudoporphyria is a photodistributed bullous disorder. […] Diagnostic testing for porphyrias should be performed in individuals who present with severe, diffuse neuropathic abdominal pain and accompanying symptoms and in individuals with cutaneous photosensitivity.

• #109 Porphyrias | Choose the Right Test

  https://arupconsult.com/content/porphyrias

  Erythrocyte porphyrin analysis is the first-line test for evaluating patients for suspected protoporphyrias (EPP or XLP), which are characterized by elevated protoporphyrin levels. […] After laboratory testing has identified the type of porphyria, additional testing of enzymes and/or variants may help confirm the diagnosis.

• #110 Porphyrias | Choose the Right Test

  https://arupconsult.com/content/porphyrias

  Erythrocyte porphyrin analysis is the first-line test for evaluating patients for suspected protoporphyrias (EPP or XLP), which are characterized by elevated protoporphyrin levels. […] After laboratory testing has identified the type of porphyria, additional testing of enzymes and/or variants may help confirm the diagnosis.

• #111 Porphyrias | Choose the Right Test

  https://arupconsult.com/content/porphyrias

  The porphyrias are caused by loss (or gain, in the case of X-linked erythropoietic protoporphyria [XLP]) of specific enzyme functions in the heme biosynthesis pathway. […] Initial testing includes porphobilinogen (PBG) measurement, urine porphyrin fractionation, and erythrocyte protoporphyrin measurements. […] Genetic testing can provide definitive diagnosis but is usually not required. […] Patients with acute hepatic porphyrias are at greater risk for hepatic fibrosis or cirrhosis, as well as hepatocellular carcinoma (HCC). […] Pseudoporphyria is a photodistributed bullous disorder. […] Diagnostic testing for porphyrias should be performed in individuals who present with severe, diffuse neuropathic abdominal pain and accompanying symptoms and in individuals with cutaneous photosensitivity.

• #112 Porphyria (Chapter 32) – The Causes of Epilepsy

  https://www.cambridge.org/core/books/causes-of-epilepsy/porphyria/6EC9E4AFB480DC4373E59EE412302D0D

  The porphyrias are a group of conditions in which there are deficiencies in one of the eight enzymes of the heme biosynthetic pathway (the porphyrin pathway): four of the enzymes are located in the mitochondria and the other four in the cytosol. There are three acute porphyrias which cause epilepsy and other neurological symptoms: acute intermittent porphyria (AIP), variegate porphyria, and hereditary coproporphyria (HCP). […] The diagnosis of acute porphyria depends on demonstrating increased levels of urinary d-aminolevulinic acid (ALA) and porphobilinogen (PBG) in urine. Genetic testing can confirm the disease, but as there are many different mutations in the PBGD gene it is not used widely for screening purposes. […] Non-enzyme-inducing drugs such as gabapentin, pregabalin, topiramate, or levetiracetam are much safer. For acute therapy, diazepam and clonazepam are relatively safe. Magnesium sulfate has also traditionally been used.

• #113 Acute Intermittent Porphyria – Symptoms, Triggers, & Causes

  https://panhematin.com/about-aip/

  AIP is caused by a partial lack of activity of an enzyme known as porphobilinogen deaminase (PBGD). […] If you have AIP, you have about half of the normal amount of PBGD enzyme activity in your body. […] The build-up of these toxic or harmful molecules causes the symptoms that occur during an AIP attack. […] AIP attacks can be very serious. […] Untreated attacks can cause serious damage to your nervous system including paralysis, and even death. […] Early diagnosis and treatment of AIP are critical. […] AIP is rare and symptoms are nonspecific. […] Attacks can also be triggered by starting a new prescription drug. […] Certain prescription drugs.

• #114 Causes of PorphyriasEnvelope icon

  https://porphyrianews.com/causes-of-porphyrias/

  Porphyrias are a group of genetic disorders that are caused by disruptions in heme production. […] Each type of porphyria stems from the loss of a specific enzyme necessary for heme production. […] Porphyrias result from the combination of genetic and environmental triggers. […] The genetic mutations associated with porphyrias — often considered more as predisposing factors than outright causes — can be inherited in one of three manners: autosomal recessive, autosomal dominant, or X-linked. […] Although inherited genetic mutations underlie all porphyrias, not everyone carrying these mutations will experience symptoms. […] Common triggers for porphyrias include excessive alcohol consumption, sunlight exposure, use of certain medications, stress, and fasting. […] The extremely rare X-linked protoporphyria (XLP) arises from mutations in the ALAS2 gene.

• #115 What is Porphyria? | Porphyria NewsEnvelope icon

  https://porphyrianews.com/what-is-porphyria/

  Porphyria comprises a group of genetic disorders caused by disruptions in the heme production cycle. […] Mutations in the genes encoding each enzyme involved in heme production underlie each type of porphyria. […] Simply carrying a mutation, however, does not guarantee that symptoms will develop. Mutations are often seen as predisposing factors, while additional environmental factors are typically needed to trigger the disease. Common environmental factors that may act as triggers for porphyria include heavy alcohol use, sunlight exposure, certain medications and recreational drugs, stress, fasting, and hormonal changes associated with menstruation and menopause.

• #116 What is Porphyria? | Porphyria NewsEnvelope icon

  https://porphyrianews.com/what-is-porphyria/

  Porphyria comprises a group of genetic disorders caused by disruptions in the heme production cycle. […] Mutations in the genes encoding each enzyme involved in heme production underlie each type of porphyria. […] Simply carrying a mutation, however, does not guarantee that symptoms will develop. Mutations are often seen as predisposing factors, while additional environmental factors are typically needed to trigger the disease. Common environmental factors that may act as triggers for porphyria include heavy alcohol use, sunlight exposure, certain medications and recreational drugs, stress, fasting, and hormonal changes associated with menstruation and menopause.

• #117 Hepatic Porphyria | Conditions | UCSF Health

  https://www.ucsfhealth.org/conditions/hepatic-porphyria

  Treatment for hepatic porphyria focuses on avoiding triggers such as alcohol consumption or too much iron in the body that lead to symptoms. […] Treatment for hepatic porphyria depends on the type. However, for both cutaneous and acute porphyria, the first step of therapy involves identifying and eliminating the precipitating factors, such as alcohol, certain medication or excess iron. […] For patients with cutaneous porphyria whose iron levels are high, iron depletion is recommended. […] The best form of treatment for acute porphyria is prevention. […] When acute porphyria progresses despite elimination of triggering factors, hospitalization is necessary. Specific treatment involves administration of intravenous hematin, which compensates for the genetic deficiency.

• #118 What Hematologists Need to Know About Acute Hepatic Porphyria – Hematology & Oncology

  https://www.hematologyandoncology.net/archives/november-2016/what-hematologists-need-to-know-about-acute-hepatic-porphyria/

  The porphyrias encompass a group of inherited metabolic disorders that result from a deficiency of one of the enzymes in the heme biosynthetic pathway. These are genetic disorders; they can be inherited in an autosomal dominant or recessive X-linked pattern; or they may be sporadic, as with porphyria cutanea tarda. […] Because these are almost always autosomal dominant disorders, patients have approximately half-normal enzyme activity. Under normal circumstances, this is sufficient for heme synthesis. The presence of certain precipitating factors, however, can lead to symptomatic disease. The most common precipitating factors are drugs, fasting, hormonal changes, stress, and illness. Women are much more likely than men to manifest symptoms, presumably because of hormonal factors. […] A genetic change leads to a deficiency in one of the enzymes in the heme biosynthetic pathway. […] The biochemical and other results from this study allowed us to confirm that ALAS1 mRNA is significantly increased in patients with acute attacks, and that ALA and PBG are the primary mediators of acute attacks.

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