Materiały źródłowe

• #1 A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5343975/

  Gaucher disease (GD, ORPHA355) is a rare, autosomal recessive genetic disorder. It is caused by a deficiency of the lysosomal enzyme, glucocerebrosidase, which leads to an accumulation of its substrate, glucosylceramide, in macrophages. […] The main cause of the cytopenia, splenomegaly, hepatomegaly, and bone lesions associated with the disease is considered to be the infiltration of the bone marrow, spleen, and liver by Gaucher cells. […] Gaucher disease (GD, OMIM #230800, ORPHA355) is the most common sphingolipidosis. It was first described by Philippe Gaucher in 1882 in a patient with massive splenomegaly without leukemia. GD is a rare, autosomal, recessive genetic disease caused by mutations in the GBA1 gene, located on chromosome 1 (1q21). This leads to a markedly decreased activity of the lysosomal enzyme, glucocerebrosidase (GCase, also called glucosylceramidase or acid -glucosidase, EC: 4.2.1.25), which hydrolyzes glucosylceramide (GlcCer) into ceramide and glucose.

• #1 What Is Gaucher Disease? | National Gaucher Foundation

  https://www.gaucherdisease.org/about-gaucher-disease/what-is/

  Gaucher disease is a genetic disorder where fat-laden Gaucher cells build up in areas like the spleen, liver and bone marrow. A person will get Gaucher Disease if both parents are carriers of the disease. […] Gaucher disease is caused by low levels of glucocerebrosidase (GCase), an enzyme that breaks down a fatty chemical in the body called glucocerebroside. Gaucher cells are normal scavenger cells called macrophages that become full of unprocessed glucocerebroside. […] When both parents are carriers, each pregnancy has a 1 in 4 chance that the baby will be born with the disease.

• #1 A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5343975/

  Very rarely, GD can also be caused by a deficiency in the GCase activator, saposin C. […] The phenotype is variable, but three clinical forms have been identified: type 1 is the most common and typically causes no neurological damage, whereas types 2 and 3 are characterized by neurological impairment. […] Mutations in the GBA1 gene lead to a marked decrease in GCase activity. The consequences of this deficiency are generally attributed to the accumulation of the GCase substrate, GlcCer, in macrophages, inducing their transformation into Gaucher cells. […] Very rarely, GD may be caused by a mutation in the PSAP gene, leading to a deficiency in saposin C without GCase deficiency. […] Patients with type-1 GD but also carriers of GBA1 mutation have been found to be predisposed to developing Parkinson’s disease, and the risk of neoplasia associated with the disease is still subject to discussion.

• #1 Gaucher Disease Clinical Presentation: History, Physical, Causes

  https://emedicine.medscape.com/article/944157-clinical

  All three forms of Gaucher disease are caused by deficient glucocerebrosidase activity due to mutations in GBA1, the structural gene that encodes the enzyme. Widespread accumulation of glucosylceramide-laden macrophages results from the enzyme deficiency. […] More than 400 different mutant GBA1 alleles have been identified in patients with Gaucher disease. Screening for the 6 most common GBA1 mutations in patients of Ashkenazi Jewish descent has enabled the identification of up to 90% of the mutant alleles in this population, but overall, a large number of other mutations have been described in other populations, complicating mutation screening. Screening may also miss alleles with more than one mutation on the same allele. Furthermore, atypical cases have been described that arise from Saposin C deficiency, uniparental isodisomy or new mutations.

• #1 Gaucher Disease Types, Genetic Causes, Symptoms, Treatment

  https://www.medicinenet.com/gaucher_disease/article.htm

  Gaucher disease is due to a genetic defect in a gene known as GBA1. […] All of the types of Gaucher disease are caused by a deficiency of the enzyme glucocerebrosidase, leading to an abnormal buildup of fatty substances, glycolipids, in the body cells. […] Mutations in the gene known as GBA1 are the cause of the deficient enzyme, and over 300 different GBA1 mutations have been identified in people with Gaucher disease. […] The four most common mutations of the GBA1 gene are N370S, L444P, 84gg, and IVS2[+1].

• #1 Gaucher Disease Clinical Presentation: History, Physical, Causes

  https://emedicine.medscape.com/article/944157-clinical

  Some mutations derive from recombination with the glucocerebrosidase pseudogene, a sequence 16 kb downstream that shares 96% sequence homology to glucocerebrosidase. Complex alleles with regions of pseudogene sequence, have been identified in some patients, but may be missed by those not familiar with the genetic architecture of the region. […] Genotype/ phenotype correlations have been noted in some specific Gaucher presentations. For example, patients with type 1 Gaucher disease who are homozygous for the N370S mutation tend to have a later onset and a relatively mild course, and patients with type 3 Gaucher disease who are homozygous for the D409H mutation exhibit a rare phenotype (Gaucher disease 3C, GD3C) that involves cardiac calcifications, oculomotor abnormalities, and corneal opacities. However, clinical presentation in patients with Gaucher disease widely varies and frequently cannot be fully explained by the underlying mutations, as severity can vary even among siblings who have identical genotypes.

• #1 Gaucher disease – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/gauchers-disease/symptoms-causes/syc-20355546

  Gaucher disease is passed along in an inheritance pattern called autosomal recessive. Both parents must be carriers of a Gaucher changed (mutated) gene for their child to inherit the condition. […] To have an autosomal recessive disorder, you inherit two changed genes, sometimes called mutations. You get one from each parent. Their health is rarely affected because they have only one changed gene. Two carriers have a 25% chance of having an unaffected child with two unaffected genes. They have a 50% chance of having an unaffected child who also is a carrier. They have a 25% chance of having an affected child with two changed genes. […] People of Eastern and Central European Jewish (Ashkenazi) ancestry are at higher risk of developing the most common variety of Gaucher disease.

• #1 Gaucher’s disease: Causes, treatment, and outlook

  https://www.medicalnewstoday.com/articles/263370

  Gauchers disease results from a hereditary enzyme deficiency. […] Gauchers disease happens because of a recessive mutation in a gene called GBA. GBA is located on chromosome 1. […] Humans normally have two copies of the genes that tell the body to produce the enzyme glucocerebrosidase, and both copies work correctly. […] If one copy is faulty, the person will not develop Gauchers disease, because just one functioning gene can produce enough of the enzyme. […] A carrier can pass on the gene but not necessarily the disease.

• #1 A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments

  https://www.mdpi.com/1422-0067/18/2/441

  Very rarely, GD can also be caused by a deficiency in the GCase activator, saposin C. […] The phenotype is variable, but three clinical forms have been identified: type 1 is the most common and typically causes no neurological damage, whereas types 2 and 3 are characterized by neurological impairment. […] The disease’s incidence is around 1/40,000 to 1/60,000 births in the general population, but it can reach 1/800 births in the Ashkenazi Jewish population. […] Mutations in the GBA1 gene lead to a marked decrease in GCase activity. […] Very rarely, GD may be caused by a mutation in the PSAP gene, leading to a deficiency in saposin C without GCase deficiency. […] Patients with a heterozygous (or homozygous) mutation in the GBA1 gene, especially c.1226A>G (N370S), but also c.1448T>C (L444P), c.84dup, c.115+1G>A (IVS2+1G>A), c.1297G>T (V394L), and c.1604G>A (R496H), are now considered at risk for Parkinson’s disease (PD).

• #1 Gaucher Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK448080/

  Gaucher disease, the most prevalent lysosomal storage disorder, presents with an elevated incidence among Ashkenazi Jews. It is an autosomal recessive inborn error of metabolism characterized by the toxic accumulation of glucocerebroside lipids within multiple organs. Gaucher disease results from mutations in the GBA1 gene, leading to deficient glucocerebrosidase activity within lysosomes. […] The underlying cause of all forms of Gaucher disease is mutations in the GBA1 gene, resulting in a lysosomal deficiency of glucocerebrosidase activity. All forms of Gaucher disease lead to the toxic accumulation of glucocerebroside lipids, primarily in the liver, spleen, and bone marrow. […] Despite knowing the precise genetic causes of most forms of Gaucher disease, the exact cause remains unknown. Patients with the same mutation can have very different signs and symptoms. It is also possible for patients with similar signs and symptoms to have very different genetic mutations. Environmental factors, as well as an individual’s particular genetic makeup, most likely influence the phenotypic expression of Gaucher disease.

• #1 Gaucher Disease – Pediatrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/pediatrics/inherited-disorders-of-metabolism/gaucher-disease

  Gaucher disease is a sphingolipidosis, an inherited disorder of metabolism, resulting from glucocerebrosidase deficiency, causing deposition of glucocerebroside and related compounds. […] Glucocerebrosidase normally hydrolyzes glucocerebroside to glucose and ceramide. Genetic defects of the enzyme cause glucocerebroside accumulation in tissue macrophages through phagocytosis, forming Gaucher cells. […] Gaucher disease is a sphingolipidosis resulting from glucocerebrosidase deficiency, causing deposition of glucocerebroside.

• #1 A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5343975/

  The pathophysiology of cancer development in GD is not well understood. At least two types of mechanisms may be operating, both of them relating to the GCase deficiency and the ensuing catabolic defect, i.e., the accumulation of GlcCer and/or its deacylated product, glucosylsphingosine or Lyso-glucosylceramide. […] The most common hypothesis is that the (perturbed) cellular and cytokinic microenvironment in GD is responsible for tumorigenesis: perturbations include markedly elevated levels of some cytokines and chemokines, activated (M2) macrophages, abnormal responses by T lymphocytes, and a reduction of NK cells. […] The frequency of hypergammaglobulinemia and the presence of monoclonal Ig in GD are two factors which promote the emergence of multiple myeloma; the incidence of myeloma appears to be increased in GD, with a relative risk of at least 5.9.

• #1 Skeletal Disease – Gaucher Disease News

  https://gaucherdiseasenews.com/symptoms/skeletal-disease/

  Gaucher disease is characterized by the accumulation of a fat molecule called glucocerebroside inside cells. This is caused by the lack of the enzyme beta-glucocerebrosidase responsible for its breakdown. […] Research has shown that high levels of fat molecules such as glucosylsphingosine and glucosylceramide in people with Gaucher disease interfere with the activities of the osteoblasts and osteoclasts, disturbing the bone metabolism process and resulting in bone disease. […] An overactive immune system and the resulting inflammation also contribute to the damage seen in Gaucher disease. Several immune cells can influence bone growth and regeneration. Many of these immune cells, especially macrophages, are overactive in Gaucher disease patients.

• #1 Gaucher Disease: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/944157-overview

  Gaucher disease is a rare genetic disorder characterized by the deposition of glucocerebroside in cells of the macrophage-monocyte system. The disorder results from the deficiency of the enzyme glucocerebrosidase. […] The disease is best characterized as a continuum of phenotypes. The severity widely varies; some patients present in childhood with virtually all the complications of Gaucher disease, whereas others remain asymptomatic into the eighth decade of life. […] The factors that contribute to neurologic involvement in patients with types 2 and 3 disease are still unknown but may be related to the accumulation of a cytotoxic glycolipid, glucosylsphingosine, in the brain due to the severe deficiency of glucocerebrosidase activity or to neuroinflammation. […] Type 1 Gaucher disease is more common among individuals with Ashkenazi Jewish heritage, although all types are panethnic in their distribution.

• #1 Patient Information – Gaucher Disease

  https://gaucherdiseaseplatform.org/patient-information/

  However, it is generally agreed that if symptoms appear later in a persons life, the less severe the disease is likely to be. […] There is currently not a clear explanation for why Gaucher Disease affects the nervous system in some patients but not others. […] The suggestion is that in Type 1 Gaucher Disease there is enough of the enzyme, b-glucocerebrosidase, to breakdown glucocerebroside (formed from gangliosides) and protect the brain, but in Type 2 and Type 3 there is not enough of the enzyme and as a result glucocerebroside builds up and neurological issues occur. […] Another theory relates to the amounts of calcium present. It is important that the amount of calcium is well balanced to make sure that nerve cells function correctly in normal circumstances. In Gaucher Disease patients, the calcium balance is affected when glucocerebroside accumulates and this can cause neurons to die.

• #1 What Is Gaucher Disease? Symptoms, Causes, Diagnosis, Treatment, and Prevention

  https://www.everydayhealth.com/genetic-diseases/gaucher-disease/guide/

  Gaucher disease is a genetic disorder thats usually inherited. Its caused by a mutation (change) in a gene called the GBA gene, which normally provides the instructions for your body to produce the enzyme glucocerebrosidase. […] When glucocerebroside cant be broken down effectively in someone with Gaucher disease, it builds up in certain areas of the body. Disease symptoms depend on which areas of the body are affected, and how much buildup there is of this fatty substance. […] All forms of Gaucher disease are inherited in whats known as an autosomal recessive pattern, as noted by NORD. That means you need to inherit an abnormal GBA gene from both of your parents to have the disease. […] In the United States, it is far more common in people of Ashkenazi (Central or Eastern European) Jewish descent than in the general U.S. population. According to StatPearls, 6 percent of people with this background carry the mutated gene that causes Gaucher disease, compared with 0.7 to 0.8 percent of the non-Jewish population. […] Gaucher disease type 1 (nonneuropathic disease) accounts for over 90 percent of cases among people of European descent, according to NORD. […] Types 2 and 3 are uncommon but may be more prevalent than type 1 in certain countries, including Egypt, India, Japan, Poland, and Sweden.

• #1 Gaucher Disease: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/944157-overview

  Type 1 Gaucher disease may present in childhood with hepatosplenomegaly, pancytopenia, and skeletal disease, although there is striking clinical variability in disease severity. […] Type 2 Gaucher disease causes rapidly progressive neurovisceral storage disease and death during infancy or during the first years of life. […] Type 3 Gaucher disease often is a less rapidly progressive neurovisceral storage disease, but it does have the largest phenotypic variation of among the GD spectrum. Various associated clinical courses have been reported, some of which cause death in childhood or early adulthood.

• #1 Gaucher disease: Pathogenesis, clinical manifestations, and diagnosis – UpToDate

  https://www.uptodate.com/contents/gaucher-disease-pathogenesis-clinical-manifestations-and-diagnosis

  Gaucher disease (GD) is an inborn error of metabolism that affects the recycling of cellular glycolipids. Glucocerebroside (also called glucosylceramide) and several related compounds that are ordinarily degraded to glucose and lipid components accumulate within the lysosomes of cells. […] The epidemiology, pathogenesis, genetics, clinical manifestations, and diagnosis of GD are discussed here. […] GD is one of the most common lysosomal diseases. Type 1 GD (GD1) is the most prevalent type in the United States, Europe, and Israel and occurs with greater frequency in the Ashkenazi Jewish population. […] The carrier frequency in the Ashkenazi Jewish population is approximately 1 in 12, and the frequency of disease-associated genotypes is calculated at 1 in 850. […] GD2 (also called acute neuronopathic GD) has an estimated incidence of 1 in 150,000.

• #1 Azthena logo with the word Azthena

  https://www.news-medical.net/health/What-is-Gauchers-Disease.aspx

  Gauchers disease is a rare genetic disorder caused by a lack of the enzyme glucocerebrosidase. […] This enzyme deficiency causes the fatty substance glucocerebroside to build up inside the macrophages, which then become ineffective and misshapen. […] The condition leads to lung and kidney dysfunction, enlargement of the liver and spleen, bone pain and broken or fractured bones. […] This form of Gauchers disease severely affects the brain and is common among infants and babies. […] The deficient enzyme is replaced with an artificial enzyme which is administered intravenously every two weeks. […] A medication called miglustat is an oral form of medication that can interrupt the build up of glucocerebroside in cells.

• #1 Gaucher Disease Clinical Presentation: History, Physical, Causes

  https://emedicine.medscape.com/article/944157-clinical

  Similarly, the amount of residual enzymatic activity does not accurately predict disease subtype and severity, with the exception that many of the mutations identified in patients with severe type 2 Gaucher disease express little, if any, enzymatic activity in vitro. These are frequently nonsense, frame-shift, or recombinant alleles that cannot form a complete protein and are essentially null alleles.

• #1 Gaucher’s disease – Wikipedia

  https://en.wikipedia.org/wiki/Gaucher%27s_disease

  Heterozygotes for particular acid beta-glucosidase mutations carry about a five-fold risk of developing Parkinson’s disease, making this the most common known genetic risk factor for Parkinson’s. […] Cancer risk may be increased, particularly myeloma. […] The role of inflammatory processes in Gaucher disease is poorly elucidated.

• #1 Gaucher Disease: A Rare Disease Sheds Light on More Common Conditions > News > Yale Medicine

  https://www.yalemedicine.org/news/gaucher-disease-interview

  We’ve learned that this lipid, this fatty material that builds up in Gaucher disease, drives the fundamental process that harms neurons in the substantia nigra, the part of the brain that is damaged in Parkinson’s disease. […] As we create new treatments for Gaucher, we can potentially help tens of thousands of people with Parkinsons disease who are carriers of the Gaucher disease mutation.

• #1 Gaucher disease | Causes, Symptoms & Treatment | Britannica

  https://www.britannica.com/science/Gaucher-disease

  Gaucher disease is inherited as an autosomal recessive trait and is caused by one or more mutations in a gene called acid beta-glucosidase (GBA). […] These mutations result in defects in the synthesis of an enzyme called glucocerebrosidase, leading to the accumulation of lipids called glucocerebrosides in Gaucher cells. […] While the connection between Gaucher disease and Parkinson disease is unclear, researchers have postulated that the accumulation of lipids in the central nervous system that occurs in patients with Gaucher disease may cause damage to dopaminergic neurons in the brain that leads to the development of Parkinson disease.

• #1 A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments

  https://www.mdpi.com/1422-0067/18/2/441

  The pathophysiology of cancer development in GD is not well understood. At least two types of mechanisms may be operating, both of them relating to the GCase deficiency and the ensuing catabolic defect, i.e., the accumulation of GlcCer and/or its deacylated product, glucosylsphingosine or Lyso-glucosylceramide. […] The most common hypothesis is that the (perturbed) cellular and cytokinic microenvironment in GD is responsible for tumorigenesis: perturbations include markedly elevated levels of some cytokines and chemokines, activated (M2) macrophages, abnormal responses by T lymphocytes, and a reduction of NK cells. […] The second hypothesis considers that initial steps towards a catabolic defect originate not from the environment, but from the (future) malignant cell itself.

• #1

  https://www.jscreen.org/hereditary-diseases/gaucher-disease?srsltid=AfmBOoohST9EZFkogVHDtJ63dz11tKXv7G1XxTSdi-H8DuotxmHZOHl8

  Gaucher disease is a genetic disorder caused by changes in the GBA gene that affect the bodys ability to break down a substance found in cell membranes. […] Gaucher disease is a recessive genetic disorder, meaning it occurs when a child has no working copies of the GBA gene. Typically, people have two working copies of each gene. When a child has Gaucher disease, both of their parents are typically carriers, each having only a single working copy of the GBA gene. […] Type 1 Gaucher disease is the most common form of this disease. This type is particularly prevalent among people of Ashkenazi Jewish descent; approximately 1 in 800 is affected by the disease and 1 in 14 is a carrier. […] Genetic testing plays a critical role in diagnosing Gaucher disease and finding carriers. Early diagnosis allows for quicker access to treatments that can slow down the diseases progression. […] Gaucher disease is treated through enzyme replacement therapy (ERT). ERT is given by infusion twice a month and helps stop the buildup of the substances that would accumulate in the body in a person with Gaucher disease.

• #1 Lysosomal Storage Disorders: Gaucher and Fabry Disease

  https://ggc.org/gene-scene-blog/lysosomal-storage-disorders-gaucher-and-fabry-disease

  Gaucher disease is a rare genetic metabolic disorder caused by a deficiency of the enzyme glucocerebrosidase (GCase). The lack of this enzyme causes a buildup of fat known as lipids, particularly the glycolipid, glucocerebroside, throughout the body. […] Gaucher is an autosomal recessive disorder, meaning both parents must carry the altered glucocerebrosidase (GBA) gene and pass it to their child in order for them to be affected. […] There are three types of Gaucher disease. […] Blood tests can identify decreased levels of the GCase enzyme, which causes Gaucher disease. […] Genetic testing can also be performed using a blood or saliva sample to identify mutations in the GBA1 gene that causes the disease.

• #2 A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments

  https://www.mdpi.com/1422-0067/18/2/441

  Gaucher disease (GD, ORPHA355) is a rare, autosomal recessive genetic disorder. It is caused by a deficiency of the lysosomal enzyme, glucocerebrosidase, which leads to an accumulation of its substrate, glucosylceramide, in macrophages. […] The main cause of the cytopenia, splenomegaly, hepatomegaly, and bone lesions associated with the disease is considered to be the infiltration of the bone marrow, spleen, and liver by Gaucher cells. […] Gaucher disease (GD, OMIM #230800, ORPHA355) is the most common sphingolipidosis. It was first described by Philippe Gaucher in 1882 in a patient with massive splenomegaly without leukemia. GD is a rare, autosomal, recessive genetic disease caused by mutations in the GBA1 gene, located on chromosome 1 (1q21). This leads to a markedly decreased activity of the lysosomal enzyme, glucocerebrosidase (GCase, also called glucosylceramidase or acid β-glucosidase, EC: 4.2.1.25), which hydrolyzes glucosylceramide (GlcCer) into ceramide and glucose.

• #2 Gaucher Disease: Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/16234-gaucher-disease

  Gaucher disease is an inherited metabolic disorder. A genetic change (mutation) in the GBA gene causes the disease. The GBA gene is responsible for making an enzyme called glucocerebrosidase (GCase). People with Gaucher disease don’t have enough of this enzyme. […] If your body doesn’t have enough of these enzymes, fatty chemicals (called Gaucher cells) build up in your organs, bone marrow and brain. The excess fats cause a wide range of problems and symptoms. They affect how your organs work, and they destroy blood cells and weaken bones.

• #2 Azthena logo with the word Azthena

  https://www.news-medical.net/health/What-is-Gauchers-Disease.aspx

  Gauchers disease is a rare genetic disorder caused by a lack of the enzyme glucocerebrosidase. […] This enzyme deficiency causes the fatty substance glucocerebroside to build up inside the macrophages, which then become ineffective and misshapen. […] The condition leads to lung and kidney dysfunction, enlargement of the liver and spleen, bone pain and broken or fractured bones. […] This form of Gauchers disease severely affects the brain and is common among infants and babies. […] The deficient enzyme is replaced with an artificial enzyme which is administered intravenously every two weeks. […] A medication called miglustat is an oral form of medication that can interrupt the build up of glucocerebroside in cells.

• #2 A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments

  https://www.mdpi.com/1422-0067/18/2/441

  Very rarely, GD can also be caused by a deficiency in the GCase activator, saposin C. […] The phenotype is variable, but three clinical forms have been identified: type 1 is the most common and typically causes no neurological damage, whereas types 2 and 3 are characterized by neurological impairment. […] The disease’s incidence is around 1/40,000 to 1/60,000 births in the general population, but it can reach 1/800 births in the Ashkenazi Jewish population. […] Mutations in the GBA1 gene lead to a marked decrease in GCase activity. […] Very rarely, GD may be caused by a mutation in the PSAP gene, leading to a deficiency in saposin C without GCase deficiency. […] Patients with a heterozygous (or homozygous) mutation in the GBA1 gene, especially c.1226A>G (N370S), but also c.1448T>C (L444P), c.84dup, c.115+1G>A (IVS2+1G>A), c.1297G>T (V394L), and c.1604G>A (R496H), are now considered at risk for Parkinson’s disease (PD).

• #2 Gaucher disease causes | Gaucher Disease News

  https://gaucherdiseasenews.com/causes/

  Gaucher disease is a rare inherited disorder caused by genetic mutations that interfere with the body’s ability to produce an enzyme needed to break down certain fatty molecules inside cells. […] The exact causes of Gaucher disease are mutations in a gene called GBA1. […] More than 400 mutations have been identified as Gaucher disease causes, but predicting a person’s disease type or how their disease will progress based solely on their genetic mutations remains challenging. […] Because it is caused by inherited mutations, the only true Gaucher disease risk factor is having biological parents who have Gaucher disease or are carriers of the disease.

• #2 Clinical Roundtable Monograph: Disease State Awareness in Gaucher Disease: A Q&A Expert Roundtable Discussion – Hematology & Oncology

  https://www.hematologyandoncology.net/supplements/clinical-roundtable-monograph-disease-state-awareness-in-gaucher-disease-a-qa-expert-roundtable-discussion/

  Gaucher disease is an inherited lysosomal storage disorder caused by mutations in the gene that encodes the lysosomal enzyme glucocerebrosidase. […] In the case of Gaucher disease, autosomal recessive inheritance of various gene defects results in a deficiency in the lysosomal hydrolase glucocerebrosidase (acid-β-glucosidase). […] The lack of functional glucocerebrosidase causes an abnormal accumulation of the lipid glucocerebroside inside cells, primarily macrophages. […] Gaucher disease results from biallelic mutations in the glucocerebrosidase gene (GBA), which is assigned to a gene-dense region of chromosome 1q. […] To date, more than 300 mutations in the GBA gene are known that cause defects in the glucocerebrosidase enzyme. […] The N370S mutation in the GBA gene is the most frequently observed mutation among Ashkenazi Jewish patients.

• #2 Gaucher Disease > Fact Sheets > Yale Medicine

  https://www.yalemedicine.org/conditions/gaucher-disease

  Gaucher disease is a rare, inherited disorder that causes fatty substances to build up in the spleen, liver, and other organs. […] The disease is caused by the body not having enough of an important enzyme (glucocerebrosidase), which breaks down a fatty chemical (glucocerebroside). […] To have Gaucher disease, you must have two mutations of a gene called GBA: one from your mother and one from your father. […] If both parents are carriers, each pregnancy has a 1 in 4 chance that the baby will have the disease.

• #2 Gaucher disease | Beacon Health System

  https://www.beaconhealthsystem.org/library/diseases-and-conditions/gaucher-disease?content_id=CON-20248806

  Gaucher disease is passed along in an inheritance pattern called autosomal recessive. Both parents must be carriers of a Gaucher changed (mutated) gene for their child to inherit the condition. […] To have an autosomal recessive disorder, you inherit two changed genes, sometimes called mutations. You get one from each parent. Their health is rarely affected because they have only one changed gene. Two carriers have a 25% chance of having an unaffected child with two unaffected genes. They have a 50% chance of having an unaffected child who also is a carrier. They have a 25% chance of having an affected child with two changed genes.

• #2 About Gaucher Disease

  https://www.genome.gov/Genetic-Disorders/Gaucher-Disease

  Gaucher disease is caused by changes (mutations) in a single gene called GBA. Mutations in the GBA gene cause very low levels of glucocerebrosidase. A person who has Gaucher disease inherits a mutated copy of the GBA gene from each of his/her parents. […] Gaucher disease is inherited in families in an autosomal recessive manner. Normally, a person has two copies of the genes that provide instructions for making the enzyme, glucocerbrosidase. For most individuals, both genes work properly. When one of the two genes is not functioning properly, the person is a carrier. Carriers do not have Gaucher disease because they have one normally functioning gene that makes enough of the enzyme to carry out normal body functions. When an individual inherits an altered gene from each carrier parent, he or she has Gaucher disease.

• #2 Gaucher disease Information | Mount Sinai – New York

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

  Gaucher disease is a rare genetic disorder in which a person lacks an enzyme called glucocerebrosidase (GBA). […] Gaucher disease is rare in the general population. People of Eastern and Central European (Ashkenazi) Jewish heritage are more likely to have this disease. […] It is an autosomal recessive disease. This means that the mother and father must both pass one variant copy of the disease gene to their child in order for the child to develop the disease. A parent who carries one variant copy of the gene, but doesn’t have the disease, is called a silent carrier. […] The lack of GBA causes harmful substances to build up in the liver, spleen, bones, and bone marrow. These substances prevent cells and organs from working properly.

• #2 Gaucher disease | Myriad Foresight® Carrier Screen

  https://myriad.com/womens-health/diseases/gaucher-disease/

  Gaucher disease is an inherited lysosomal storage disorder caused by harmful genetic changes in the GBA1 gene, formerly known as the GBA gene. […] The condition develops when the body fails to properly produce a particular enzyme to break down a fatty substance called glucocerebroside. […] Studies have shown that carriers of Gaucher disease may have an increased risk of developing Parkinson’s disease, above the risks seen in the general population. […] The incidence of Gaucher disease is 1 in 40,000 to 1 in 60,000 in the general population. […] It is more common in people of Ashkenazi Jewish ancestry, where the incidence is approximately 1 in 800.

• #2 A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5343975/

  Gaucher disease (GD, ORPHA355) is a rare, autosomal recessive genetic disorder. It is caused by a deficiency of the lysosomal enzyme, glucocerebrosidase, which leads to an accumulation of its substrate, glucosylceramide, in macrophages. […] The main cause of the cytopenia, splenomegaly, hepatomegaly, and bone lesions associated with the disease is considered to be the infiltration of the bone marrow, spleen, and liver by Gaucher cells. […] Gaucher disease (GD, OMIM #230800, ORPHA355) is the most common sphingolipidosis. It was first described by Philippe Gaucher in 1882 in a patient with massive splenomegaly without leukemia. GD is a rare, autosomal, recessive genetic disease caused by mutations in the GBA1 gene, located on chromosome 1 (1q21). This leads to a markedly decreased activity of the lysosomal enzyme, glucocerebrosidase (GCase, also called glucosylceramidase or acid -glucosidase, EC: 4.2.1.25), which hydrolyzes glucosylceramide (GlcCer) into ceramide and glucose.

• #2 A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments

  https://www.mdpi.com/1422-0067/18/2/441

  The pathophysiology of cancer development in GD is not well understood. At least two types of mechanisms may be operating, both of them relating to the GCase deficiency and the ensuing catabolic defect, i.e., the accumulation of GlcCer and/or its deacylated product, glucosylsphingosine or Lyso-glucosylceramide. […] The most common hypothesis is that the (perturbed) cellular and cytokinic microenvironment in GD is responsible for tumorigenesis: perturbations include markedly elevated levels of some cytokines and chemokines, activated (M2) macrophages, abnormal responses by T lymphocytes, and a reduction of NK cells. […] The second hypothesis considers that initial steps towards a catabolic defect originate not from the environment, but from the (future) malignant cell itself.

• #2 Patient Information – Gaucher Disease

  https://gaucherdiseaseplatform.org/patient-information/

  However, it is generally agreed that if symptoms appear later in a persons life, the less severe the disease is likely to be. […] There is currently not a clear explanation for why Gaucher Disease affects the nervous system in some patients but not others. […] The suggestion is that in Type 1 Gaucher Disease there is enough of the enzyme, b-glucocerebrosidase, to breakdown glucocerebroside (formed from gangliosides) and protect the brain, but in Type 2 and Type 3 there is not enough of the enzyme and as a result glucocerebroside builds up and neurological issues occur. […] Another theory relates to the amounts of calcium present. It is important that the amount of calcium is well balanced to make sure that nerve cells function correctly in normal circumstances. In Gaucher Disease patients, the calcium balance is affected when glucocerebroside accumulates and this can cause neurons to die.

• #2 A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5343975/

  Very rarely, GD can also be caused by a deficiency in the GCase activator, saposin C. […] The phenotype is variable, but three clinical forms have been identified: type 1 is the most common and typically causes no neurological damage, whereas types 2 and 3 are characterized by neurological impairment. […] Mutations in the GBA1 gene lead to a marked decrease in GCase activity. The consequences of this deficiency are generally attributed to the accumulation of the GCase substrate, GlcCer, in macrophages, inducing their transformation into Gaucher cells. […] Very rarely, GD may be caused by a mutation in the PSAP gene, leading to a deficiency in saposin C without GCase deficiency. […] Patients with type-1 GD but also carriers of GBA1 mutation have been found to be predisposed to developing Parkinson’s disease, and the risk of neoplasia associated with the disease is still subject to discussion.

• #2 Gaucher Disease: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/944157-overview

  Type 1 Gaucher disease may present in childhood with hepatosplenomegaly, pancytopenia, and skeletal disease, although there is striking clinical variability in disease severity. […] Type 2 Gaucher disease causes rapidly progressive neurovisceral storage disease and death during infancy or during the first years of life. […] Type 3 Gaucher disease often is a less rapidly progressive neurovisceral storage disease, but it does have the largest phenotypic variation of among the GD spectrum. Various associated clinical courses have been reported, some of which cause death in childhood or early adulthood.

• #2 Gaucher Disease – MD Searchlight

  https://mdsearchlight.com/genetic-disorders/gaucher-disease/

  Gaucher disease is caused by changes or mutations in the GBA1 gene. This mutation causes a deficiency in an enzyme called glucocerebrosidase. […] Even though we know the genetic causes of most Gaucher diseases, we’re still unsure about the exact trigger. Patients with the same mutation can have different symptoms. And oddly, patients with similar symptoms can have very different genetic mutations. This likely means that other factors like the environment or individual genetics may influence how Gaucher disease shows up in a person.

• #3 Clinical Roundtable Monograph: Disease State Awareness in Gaucher Disease: A Q&A Expert Roundtable Discussion – Hematology & Oncology

  https://www.hematologyandoncology.net/supplements/clinical-roundtable-monograph-disease-state-awareness-in-gaucher-disease-a-qa-expert-roundtable-discussion/

  The most common GBA disease allele worldwide is the missense mutation L444P. […] The presence of L444P in diverse populations throughout the world indicates that this mutation likely arises on a recurrent basis. […] The third most frequent mutation in individuals with Gaucher disease is the insertion mutation 84GG, which leads to a frame shift and premature termination. […] The fourth most common mutation in Gaucher disease is IVS2+1, an RNA processing mutation that causes deletion of the second exon of the GBA gene. […] Together, these 4 mutations—N370S, L444P, 84GG, and IVS2+1—account for 80–90% of all mutations detected in Ashkenazi Jewish individuals with Gaucher disease and 50–60% of all mutations in the non-Jewish patient population.

• #3 Gaucher disease: Pathogenesis, clinical manifestations, and diagnosis – UpToDate

  https://www.uptodate.com/contents/gaucher-disease-pathogenesis-clinical-manifestations-and-diagnosis

  Gaucher disease (GD) is an inborn error of metabolism that affects the recycling of cellular glycolipids. Glucocerebroside (also called glucosylceramide) and several related compounds that are ordinarily degraded to glucose and lipid components accumulate within the lysosomes of cells. […] The epidemiology, pathogenesis, genetics, clinical manifestations, and diagnosis of GD are discussed here. […] GD is one of the most common lysosomal diseases. Type 1 GD (GD1) is the most prevalent type in the United States, Europe, and Israel and occurs with greater frequency in the Ashkenazi Jewish population. […] The carrier frequency in the Ashkenazi Jewish population is approximately 1 in 12, and the frequency of disease-associated genotypes is calculated at 1 in 850. […] GD2 (also called acute neuronopathic GD) has an estimated incidence of 1 in 150,000.

• #3 What Is Gaucher Disease? Symptoms, Causes, Diagnosis, Treatment, and Prevention

  https://www.everydayhealth.com/genetic-diseases/gaucher-disease/guide/

  Gaucher disease is a genetic disorder thats usually inherited. Its caused by a mutation (change) in a gene called the GBA gene, which normally provides the instructions for your body to produce the enzyme glucocerebrosidase. […] When glucocerebroside cant be broken down effectively in someone with Gaucher disease, it builds up in certain areas of the body. Disease symptoms depend on which areas of the body are affected, and how much buildup there is of this fatty substance. […] All forms of Gaucher disease are inherited in whats known as an autosomal recessive pattern, as noted by NORD. That means you need to inherit an abnormal GBA gene from both of your parents to have the disease. […] In the United States, it is far more common in people of Ashkenazi (Central or Eastern European) Jewish descent than in the general U.S. population. According to StatPearls, 6 percent of people with this background carry the mutated gene that causes Gaucher disease, compared with 0.7 to 0.8 percent of the non-Jewish population. […] Gaucher disease type 1 (nonneuropathic disease) accounts for over 90 percent of cases among people of European descent, according to NORD. […] Types 2 and 3 are uncommon but may be more prevalent than type 1 in certain countries, including Egypt, India, Japan, Poland, and Sweden.

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