Materiały źródłowe

• #1 Adrenoleukodystrophy – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/adrenoleukodystrophy/symptoms-causes/syc-20369157

  Adrenoleukodystrophy (ALD) is a type of hereditary (genetic) condition that damages the membrane (myelin sheath) that insulates nerve cells in your brain. […] In adrenoleukodystrophy (ALD), your body can’t break down very long-chain fatty acids (VLCFAs), causing saturated VLCFAs to build up in your brain, nervous system and adrenal gland. […] The most common type of ALD is X-linked ALD, which is caused by a genetic defect on the X chromosome. X-linked ALD affects males more severely than females, who carry the disease.

• #2 Adrenoleukodystrophy – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562328/

  Adrenoleukodystrophy is usually X-linked (X-ALD) and caused by over 2700 known mutations in the ABCD1 gene mutations. The ABCD1 gene plays a significant role in the VLCFA transport system into peroxisomes, where VLCFAs can undergo further metabolism. Mutations in the ABCD1 gene product interfere with this process, leading to the abnormal accumulation of VLCFAs in various body organs and interfering with their normal physiological functions. […] A similar peroxisomal syndrome, Zellweger spectrum disorder, is caused by mutations in the PTS1 receptor, PXR, or any of the many identified PEX genes. The PEX genes are involved in the formation and function of peroxisomes. One of the Zellweger spectrum disorders is neonatal adrenoleukodystrophy, which has an earlier and more severe presentation than other forms of ALD. […] Four main subtypes of adrenoleukodystrophy are described based on the organs affected and the age at presentation: neonatal, childhood cerebral, adrenomyeloneuropathy, and adrenal insufficiency.

• #3 Adrenoleukodystrophy (ALD) | Boston Children’s Hospital

  https://www.childrenshospital.org/conditions/adrenoleukodystrophy-ald

  ALD is caused by mutations in the ABCD1 gene that prevent the body from breaking down very-long-chain fatty acids (VLCFAs). As a result, VLCFAs build up in the brain, nervous system, and adrenal glands. […] CALD is caused by a mutation in the ABCD1 gene on the X chromosome. Because a female has two X chromosomes, if she inherits the faulty gene, then she still has another X chromosome to offset the mutation. However, because males only have one X chromosome, the gene abnormality causes the disease. […] Pregnant women with an ALD mutation on one of their X chromosomes have a 1 in 4 chance of having a son affected by the disease and a 1 in 4 chance of having a daughter who has the mutation on one X chromosome.

• #4 Adrenoleukodystrophy (ALD): Causes, Types, Symptoms, Prognosis

  https://www.webmd.com/brain/what-is-adrenoleukodystrophy

  About 1 in 17,000 people are born with a genetic disease called adrenoleukodystrophy (ALD). […] A mutated gene on the X chromosome (the strand of DNA that decides if you’re born male or female) is the cause of ALD. […] An inherited mutation of the ABCD1 gene causes adrenoleukodystrophy. […] Adrenoleukodystrophy (ADL) is a genetic condition in which your body is unable to break down a type of fatty acid called VLCFAs, which build up in the brain, nervous system, and adrenal glands. The most common type of ADL, X-linked adrenoleukodystrophy, comes from a mutation on the X chromosome.

• #5 Adrenoleukodystrophy: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/001182.htm

  Adrenoleukodystrophy (ALD) describes several closely related disorders that disrupt the breakdown of certain fats. These disorders are often passed down (inherited) in families. […] ALD is usually passed down from parent to child as an X-linked genetic trait. It affects mostly males. Some women who are carriers can have milder forms of the disease. It affects about 1 in 20,000 people from all races. […] Some cases of ALD occur when the gene changes on its own. This is called sporadic and is not inherited. […] The condition results in the buildup of very-long-chain fatty acids in the nervous system, adrenal gland, and testes. This disrupts normal activity in these parts of the body.

• #6 Adrenoleukodystrophy / Adrenomyeloneuropathy – National Adrenal Diseases Foundation

  https://www.nadf.us/adrenoleukodystrophy-adrenomyeloneuropathy.html

  X-linked adrenoleukodystrophy (ALD) is an inherited male-limited disorder that can affect the nervous system and the adrenal glands. Its prevalence is estimated at about 1 in 15,000-20,000 individuals, and has been diagnosed more often since the advent of newborn screening for ALD. […] ALD is in the class of peroxisomal storage diseases, and is caused by mutations in the ABCD1 gene that codes for a protein known as ALD protein (ALDP). A deficiency of ALDP prevents breakdown of very long chain fatty acids (VLCFA). The accumulation of VLCFA triggers an inflammatory reaction and consequent destructive changes in the adrenal cortex and brain myelin. […] Genetic testing and counseling should be offered to families of ALD patients. Women, because they carry two X chromosomes (of which only one is usually affected with the ABCD1 mutation), are protected from developing severe forms of ALD. Women carriers transmit the X-linked ALD trait to half their sons. Any male with adrenal insufficiency or unexplained neurologic problems should be tested for ALD.

• #7 X-linked adrenoleukodystrophy: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/x-linked-adrenoleukodystrophy/

  X-linked adrenoleukodystrophy is a genetic disorder that mainly affects the nervous system and the adrenal glands, which are located on top of each kidney. […] Variants (also known as mutations) in the ABCD1 gene cause X-linked adrenoleukodystrophy. […] The ABCD1 gene provides instructions for producing the adrenoleukodystrophy protein (ALDP), which is involved in transporting certain fat molecules called very long-chain fatty acids (VLCFAs) into peroxisomes. […] ABCD1 gene variants result in a shortage (deficiency) of ALDP. […] When this protein is lacking, the transport and subsequent breakdown of VLCFAs is disrupted, causing abnormally high levels of these fats in the body. […] The accumulation of VLCFAs may be toxic to the adrenal cortex and myelin. […] Research suggests that the accumulation of VLCFAs triggers an inflammatory response in the brain, which could lead to the breakdown of myelin. […] The destruction of these tissues leads to the signs and symptoms of X-linked adrenoleukodystrophy.

• #8 What Is Adrenoleukodystrophy? – Adrenoleukodystrophy News

  https://adrenoleukodystrophynews.com/what-is-adrenoleukodystrophy/

  Adrenoleukodystrophy (ALD) is caused by a mutation in the ABCD1 gene, which is located on the X-chromosome. Several mutations in the ABCD1 gene are known to cause ALD; in some patients, parts of the gene are deleted. […] The insufficient transport of VLCFAs into peroxisomes leads to an abnormal buildup of VLCFA in the blood and central nervous system. […] The exact mechanism by which VLCFAs cause damage is not entirely understood, but they appear to be toxic to the myelin sheath and the adrenal cortex or the outer layer of the adrenal gland. […] Research suggests that the accumulation of VLCFAs triggers an inflammatory response in the brain that leads to the breakdown of myelin (demyelination). […] Damage to the adrenal cortex causes a shortage of steroid hormones (mainly cortisol and aldosterone), a phenomenon known as adrenal insufficiency or Addison’s disease.

• #9 Cerebral Adrenoleukodystrophy – Child Neurology Foundation

  https://www.childneurologyfoundation.org/disorder/cerebral-adrenoleukodystrophy/

  Cerebral ALD is caused by a mutation in the ABCD1 gene. This gene helps break down very-long-chain fatty acids (VLCFAs). Because of the mutation, VLCFAs do not properly break down. They instead accumulate in the bodys tissues. […] Cerebral ALD is also called an X-linked condition. This is because it results from a problem on the X-chromosome. Females have two X-chromosomes. If a female inherits one faulty gene, she will still have one normal gene. Females are often carriers. They will have no or very mild symptoms for this reason. However, males only have one X-chromosome. Therefore, the gene mutation causes more severe disease in males. […] Cerebral ALD can be inherited from one or both parents. A male carrier should not be able to pass on this gene unless he is very mildly affected. This is not common. With each pregnancy, a female carrier (one normal X chromosome and one abnormal chromosome with the ABCD1 gene mutation) has a 50% chance of passing the abnormal gene to their child. Specifically, a female carrier has one X chromosome with an abnormal gene. Therefore, if the fetus/baby is a boy, he has a 50% chance of having ALD. A girl baby (with two X chromosomesone from the father and one from the mother) would have a 50% chance of being a carrier of the gene for cerebral ALD.

• #10 Adrenoleukodystrophy (ALD) | Great Ormond Street Hospital

  https://www.gosh.nhs.uk/conditions-and-treatments/conditions-we-treat/adrenoleukodystrophy/

  ALD is one of a group of disorders caused by a defect of peroxisomes, which are essential for the breakdown of very long chain fatty acids in cells. […] In ALD the process of transporting the very long chain fatty acids into the peroxisomes is faulty. This results in the damage to the adrenal glands, and the nerves of the spinal cord, and the myelin of the brain cells (the substance around nerve fibres that is essential for transmission of messages between brain cells and the rest of the body). It is not fully understood why the damage occurs. […] ALD is a genetic or inherited disorder. It is an X-linked recessive disorder. The ABCD1 gene is located on the X chromosome, which is one of the sex chromosomes. […] A boy with ALD will usually have inherited the faulty X-chromosome from his mother, although occasionally the genetic change occurs for the first time in the baby (a de novo genetic change). […] If a male with ALD has a child, any male children will be unaffected as only the Y chromosome is passed on from father to son, while all female children will inherit the faulty X-chromosome and ABCD1 gene and so be a carrier for ALD.

• #11 What is ALD? – ALD Alliance

  https://www.aldalliance.org/what-is-ald.html

  Adrenoleukodystrophy, or ALD, is a deadly genetic disease that affects 1 in 17,000 people. […] ALD is caused by mutations in ABCD1, a gene located on the X chromosome that codes for ALD, Protein (ALDP), which functions as a peroxisomal membrane transporter. […] ALD disease is a genetic, or inherited, disorder. If a mother is a carrier of ALD, there is a 50% chance of passing this on to her children. […] Spontaneous mutations are another way a baby can inherit ALD. This means that the mother and father are not carriers of ALD, but the mutation of the gene causing ALD happens in utero. […] The damaged gene that causes ALD resides on the X Chromosome. Boys inherit only one X Chromosome, which is passed to them from their mothers. Because girls inherit two X Chromosomes, one from each parent, the functional copy inherited from their father usually protects female children from the disease. However, females with the mutation are carriers who can pass the disease on to their male offspring. It is possible but rare for girls to inherit 2 copies of the mutation from both parents.

• #12 Adrenoleukodystrophy | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/pediatric-cerebral-adrenoleukodystrophy

  Adrenoleukodystrophy (ALD) is a rare X-linked genetic disorder that affects the brain and adrenal glands (small glands that produce important hormones in the body). […] ALD is a rare genetic condition caused by genetic variants in the ABCD1 gene, which prevent the body from transporting very-long-chain fatty acids (VLCFAs) into the part of the cell that breaks them down (peroxisomes). […] As a result, VLCFAs build up in the blood, brain, nervous system, and adrenal glands.

• #13 Adrenoleukodystrophy (ALD) |

  https://www.huntershope.org/family-care/leukodystrophies/adrenoleukodystrophy/

  Adrenoleukodystrophy is a genetic, or inherited, disorder. If a mother is a carrier of ALD, there is a 50% chance of passing this on to her children. If a father is a carrier of ALD, he will pass this on to his daughter. […] Spontaneous mutations are another way a baby can inherit ALD. This means that the mother and father are not carriers of ALD, however, the mutation of the gene causing ALD happens in utero. Spontaneous mutations arise from a variety of sources, including errors in DNA replication, spontaneous lesions, and transposable genetic elements. […] Mutations in ABCD1, a gene located on the X chromosome that codes for ALD Protein (ALDP), is responsible for causing adrenoleukodystrophy. This gene functions as a peroxisomal membrane transporter. The transporter is required for the normal turn over, or metabolism, of fatty acids in the brain and spinal cord. Without the transporter, the normal metabolism of fatty acids does not occur. Therefore, the brain and spinal cord undergo demyelination. Biochemically, individuals with ALD show very high levels of unbranched, saturated, very long chain fatty acids, particularly cerotic acid.

• #14 Adrenoleukodystrophy – The Oncofertility Consortium

  https://oncofertility.msu.edu/non-malignant-conditions/adrenoleukodystrophy/

  X-ALD is an X-linked recessive inherited condition that primarily affects males (females are carriers). It is due to mutations in ABCD1, a gene located on the X chromosome, which codes for adrenoleukodystrophy protein (ALDP), an integral peroxisomal membrane protein that transports VLCFacyl-CoA esters from the cytosol into the peroxisome. […] Mutations in ABCD1 lead to abnormal accumulation of saturated unbranched very long chain fatty acids (VLCFAs). […] This accumulation is toxic in all tissues and causes oxidative stress and oxidative damage to proteins, microglial activation, and apoptosis. […] The accumulation is greatest in nervous tissue white matter, adrenal cortex, testis, and in some lipid fractions (e.g. cholesterol esters of the adrenal gland and brain).

• #15 Causes of Adrenoleukodystrophy – Adrenoleukodystrophy News

  https://adrenoleukodystrophynews.com/adrenoleukodystrophy-causes/

  Adrenoleukodystrophy (ALD) is a severe inherited disorder that mainly affects males. […] the underlying cause of the disease is the same in each type: a mutation, or a change, in the ABCD1 (ATP binding cassette subfamily D member 1) gene. […] A wide range of mutations in ABCD1 have been identified in patients. […] Currently, there is no known correlation between the type of mutation and the severity of the disease. […] In patients with ALD, little or no functional ALDP results in insufficient transport of VLCFAs into the peroxisome and a reduction in their breakdown. […] The exact mechanism behind how high levels of VLCFAs cause damage is unknown, but ongoing research has identified potential mechanisms. […] It is thought that high levels of VLCFAs in the brain are associated with the increased production of cytokines, immune proteins that trigger inflammation.

• #16 Causes of Adrenoleukodystrophy – Adrenoleukodystrophy News

  https://adrenoleukodystrophynews.com/adrenoleukodystrophy-causes/

  Furthermore, increased VLCFAs levels may destabilize mitochondrial membranes in brain cells. […] Similarly, in the adrenal glands, the accumulation of VLCFAs may cause mitochondrial dysfunction and lead to progressive cell death. […] ALD is more common in males, who are also more likely to have severe symptoms than women. […] This is because the ABCD1 gene is located on the X chromosome, one of the two sex chromosomes that play a part in determining gender. […] Men only have one X chromosome, which means that if the ABCD1 gene it carries is mutated, then the man will develop ALD. […] Women have two X chromosomes, which means that they have two copies of ABCD1.

• #17 Understanding Adrenoleukodystrophy (ALD) | It Might Be ALD

  https://www.itmightbeald.com/understanding-ald

  Adrenoleukodystrophy (ALD) is a rare genetic disease that can progress to a serious and life-threatening condition. ALD is a genetic disease caused by mutations in the ABCD1 gene, that results in a deficiency of the peroxisomal protein called adrenoleukodystrophy protein (ALDP). This deficiency leads to the accumulation of very-long chain fatty acids (VLCFAs) in plasma and tissue primarily of the nervous system and adrenal glands. […] Because this disorder results from mutations in a gene on the X chromosome, males are more susceptible; it affects approximately 1 in 21,000 males. […] ALD is a genetic disorder, so once it is diagnosed, it’s important to test other family members, as well. […] Adrenal insufficiency is often the first symptom of ALD; up to 86% of boys diagnosed with ALD also have adrenal insufficiency.

• #18 Understanding Adrenoleukodystrophy (ALD) | It Might Be ALD

  https://www.itmightbeald.com/understanding-ald

  Adrenal insufficiency is a prominent symptom of ALD; up to 86% of boys diagnosed with ALD also have adrenal insufficiency. […] Because early symptoms of ALD often resemble those of other medical conditions, such as Addison’s disease, there can be difficulty in differential diagnosis. […] Diagnosing cerebral ALD can be difficult as the cognitive symptoms often resemble those of other conditions, such as attention-deficit/hyperactivity disorder (ADHD), autism or other home and school problems, which can delay diagnosis. […] Approximately 40% of boys with ALD will develop cerebral ALD.

• #19 Adrenoleukodystrophy – MD Searchlight

  https://mdsearchlight.com/genetic-disorders/adrenoleukodystrophy/

  Adrenoleukodystrophy (ALD) is a rare genetic disorder that causes trouble breaking down very long-chain fatty acids (VLCFAs). […] The buildup is caused by mutations in the ABCD1 gene, which usually helps transport and break down VLCFAs. […] X-ALD disease is related to a change in the ABCD1 gene. […] When the ABCD1 gene changes, it messes up this process, leading to an unhealthy build-up of VLCFA in various organs in the body. […] A change in genes named PTS1 receptor, PXR1, PEX1, PEX10, or PEX13 causes the version of the disease that appears in newborn babies. […] The four main types of X-ALD disease are the newborn version, the childhood brain version, a version that affects the nerves and adrenal gland (known as adrenomyeloneuropathy), and a version that impacts the adrenal gland.

• #20

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6031365/

  Adrenoleukodystrophy (ALD) is a fatal progressive neurodegenerative disorder affecting brain white matter. The most common form of ALD is X-linked (X-ALD) and results from mutation of the ABCD1-encoded very-long-chain fatty acid (VLCFA) transporter. […] Diagnosed in boys usually between the ages of 4 and 8 years, cerebral X-ALD symptoms progress rapidly (in as little as 2 years) through declines in cognition, learning and behavior, to paralysis and ultimately to a vegetative state and death. […] Currently, there are no good treatments for X-ALD. […] With respect to disease etiology, it is thought that VLCFA accumulation is toxic to the adrenal gland and to the myelin sheath that surrounds the many nerve cells of the body. […] However, several inconsistencies exist in patient studies that refute this model.

• #21

  https://content.govdelivery.com/accounts/MTDPHHS/bulletins/3b06c81

  X-ALD is a genetic disorder that is a form of leukodystrophy and affects approximately 1 in 15,000 individuals. This disorder mainly affects the nervous system and the adrenal glands by causing demyelination of the nerves in the brain and spinal cord. This impacts the ability of the nerves to relay signals to the brain. Damage to the adrenal cortex also causes adrenocortical insufficiency. This may cause weakness, weight loss, skin changes, vomiting, and coma. […] There are four distinct types of X-linked adrenoleukodystrophy: a childhood cerebral form, an adrenomyeloneuropathy (AMN) type, an adrenal insufficiency only form, and a type called asymptomatic. The childhood form typically occurs in boys. Untreated children experience learning and behavioral problems that begin between the ages of 4 and 10 and worsen over time, causing difficulty reading, writing, understanding speech and comprehension, aggressive behavior, vision problems, difficulty swallowing, poor coordination, and impaired adrenal gland function. Progression of this disorder can be rapid, leading to total disability within a few years. The life expectancy for this form varies, but without treatment individuals with the childhood cerebral form only survive a few years after the onset of symptoms.

• #22 Our Focus: Cerebral Adrenoleukodystrophy (CALD) | bluebird bio

  https://www.bluebirdbio.com/our-focus/cerebral-adrenoleukodystrophy

  Cerebral adrenoleukodystrophy or CALD is a rare and devastating neurologic disease that robs young patients of the chance to live a full life. […] Adrenoleukodystrophy (ALD) is a rare, X-linked, metabolic disorder caused by a mutation in the ABCD1 gene which results in the toxic buildup of very long-chain fatty acids (VLCFA) in the brain and spinal cord. […] The accumulation of VLCFA in the adrenal cortex and white matter of the brain and spinal cord leads to the progressive destruction of myelin, the protective sheath of the nerve cells in the brain that are responsible for thinking and muscle control. […] ALD is estimated to affect 1 in 5,000 to 1 in 17,000 newborns (both male and female), and approximately 1 in 20,000 to 1 in 30,000 newborn males. […] There is currently no way to predict which children with ALD will develop CALD.

• #23 What is Adrenoleukodystrophy (ALD)? | ALD Connect

  https://aldconnect.org/what-is-ald/

  Adrenomyeloneuropathy (AMN) is the most common form of adrenoleukodystrophy (ALD). It affects adult men, typically presenting with a gradual onset of stiffness and weakness in the legs, difficulty with walking, and pain or discomfort due to nerve damage. […] Most women with a genetic mutation in the ABCD1 gene will develop myeloneuropathy in adulthood, with an average age of symptom onset of around 40 years of age. Symptoms similar to those in men with AMN are common, including gait disturbances, pain, and bowel and bladder dysfunction.

• #24 X-linked adrenoleukodystrophy (X-ALD): clinical presentation and guidelines for diagnosis, follow-up and management | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-7-51

  X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder. The disease is caused by mutations in the ABCD1 gene that encodes the peroxisomal membrane protein ALDP which is involved in the transmembrane transport of very long-chain fatty acids (VLCFA; C22). […] It is caused by mutations in the ABCD1 gene located on the X-chromosome. […] X-ALD is caused by mutations in the ABCD1 gene located on the X-chromosome. So far, 600 different mutations have been identified. ABCD1 encodes ALDP, a peroxisomal transmembrane protein involved in the transport of VLCFA-CoA esters from the cytosol into the peroxisome. ALDP deficiency leads to impaired VLCFA beta-oxidation (about 30% of normal) and the accumulation of VLCFA-CoA esters in cells. […] The neuropathological hallmark of AMN is an axonopathy with microgliosis but without significant myelin changes. It is therefore likely that the primary consequence of VLCFA accumulation impairs the capacity of oligodendrocytes and Schwann cells to sustain axonal integrity, resulting in axonal damage.

• #25 Adrenoleukodystrophy | Causes, Symptoms and Treatment Guide

  https://fitwellhub.pk/adrenoleukodystrophy/

  ALD is characterized by a defect or decrease in the number of these organelles and, as such, causes an inability to effectively metabolize VLCFAs. Consequently, these fatty acids accumulate, destroying myelin sheath resulting in reduced nerve function. […] The brain and adrenal glands suffer from an excess amount of VLCFAs as a result of the abnormal ABCD1 gene. These fatty acids can be toxic to neurons and myelin which eventually lead to demyelination within the central nervous system and adrenal insufficiency. It also disturbs normal cellular processes leading to neurological as well as endocrine symptoms associated with ALD. […] VLCFAs damage adrenal glands resulting in adrenal insufficiency experienced by most patients with ALD. This failure leads to insufficient production of vital hormones like cortisol and aldosterone causing weight loss, fatigue, hypertension, etc. It is important to manage adrenal inadequacy for the well-being of the patient and to control symptoms.

• #26 Steven’s story: Living with adrenoleukodystrophy – EURORDIS-Rare Diseases Europe

  https://www.eurordis.org/stories/stevens-story-living-with-adrenoleukodystrophy/

  Steven believes that all men with adrenal insufficiency where the cause is unknown (idiopathic Addisons disease) should also be tested for adrenoleukodystrophy (ALD). […] Adrenoleukodystrophy is a rare, genetic condition that causes progressive deterioration in young boys, eradicating their ability to walk, talk and eat unaided. […] The majority of those with ALD also have Addisons disease, yet a diagnosis of idiopathic Addisons disease often does not prompt testing for ALD in adults. […] People with ALD are unable to metabolise VLCFAs, so it is often used as an initial diagnostic test for ALD. […] ALD is inherited through the X chromosome, meaning Stevens daughters, as all daughters of affected men, are carriers of ALD. […] The majority of ALD and AMN patients have Addisons disease, and while testing children with Addisons disease for ALD is common practice, this does not seem to be the case with adult males. In many cases this testing could save lives.

• #27 SSA – POMS: DI 23022.465 – Neonatal Adrenoleukodystrophy – 08/25/2020

  https://secure.ssa.gov/apps10/poms.nsf/lnx/0423022465

  Neonatal Adrenoleukodystrophy (NALD) is a leukodystrophy that causes damage to the myelin sheath, an insulating membrane that surrounds nerve cells in the brain (white matter). NALD also affects the adrenal glands and the testes. NALD belongs to the Zellweger spectrum of peroxisome biogenesis disorders (PDB, ZSS), is considered a moderately severe form and is caused by a mutation of several PEX genes. […] The condition is often slowly progressive and may include degeneration of the myelin leading to loss of previously acquired skills and ultimately death.

• #28 Adrenoleukodystrophy: Types, symptoms, inheritance, and more

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

  Adrenoleukodystrophy is a rare condition associated with abnormalities in myelin, the white matter that protects nerve fibers in the spinal cord and brain. It occurs due to a mutation on the X chromosome. […] In most cases, adrenoleukodystrophy is an X-linked recessive condition. This means a person can inherit the condition from a genetic mutation on the X chromosome that their parent carries. […] More specifically, the gene involved is ABCD1. This gene plays a role in the very-long-chain fatty acids (VLCFA) transport system and interferes with the metabolism of VLCFA. This leads to an abnormal buildup of VLCFAs in vital organs, such as the brain and spinal cord. […] N-ALD may have an autosomal recessive inheritance pattern. N-ALD interferes with any of the PTS1 receptors, including PXR 1, PEX1, PEX 10, or PEX 13 genes.

• #29 Orphanet: Neonatal adrenoleukodystrophy

  https://www.orpha.net/en/disease/detail/44

  PBD-ZSS is caused by mutations in one of 13 PEX genes encoding peroxins. Mutations in these genes lead to abnormal peroxisome biogenesis. […] The main differential diagnoses include Usher syndrome I and II, other PBD-ZSS disorders, single enzyme defects in peroxisome fatty acid beta-oxidation, and disorders that feature severe hypotonia, neonatal seizures, liver dysfunction or leukodystrophy. X-linked adrenoleukodystrophy should not be confused with NALD.

• #30 X-Linked Adrenoleukodystrophy: Symptoms, Causes, and Treatment

  https://www.healthline.com/health/x-linked-adrenoleukodystrophy

  X-linked adrenoleukodystrophy is a rare genetic condition that causes problems with the white matter in your nervous system and adrenal glands. […] X-linked adrenoleukodystrophy (X-ALD) is a genetic condition passed through families on the X chromosome. […] People with X-ALD develop degeneration of the white matter in their brain, spinal cord, and adrenal glands due to a mutation of the ABCD1 gene. This mutation leads to an inability to break down very long-chain fatty acids (VLCFAs). […] An ABCD1 gene mutation on your X chromosome causes X-ALD. […] Associated ABCD1 mutations cause a type of fat called VLCFAs to accumulate in your nervous system and adrenal glands. […] Experts think that damage to myelin might occur due to an inflammatory response from your immune system.

• #31 Frequently Asked Questions | ALD Connect

  https://aldconnect.org/resources/frequently-asked-questions/

  When the VLCFAs build up in the central nervous system, they can eventually destroy the myelin sheath—the protective, insulating coating—that surrounds the nerves. If this occurs in the brain, it often leads to neurologic problems, while in the spinal cord, it can lead to difficulty walking. VLCFAs are also toxic to adrenal gland cells. The toxicity leads to those cells malfunctioning, which then causes adrenal insufficiency. […] ALD is a single gene disorder, which means that ALD is always caused by a genetic mutation in one gene, called ABCD1. The non-functional gene is usually inherited from a parent, however ALD can sometimes occur via spontaneous mutation without any family history, which is also called a de novo mutation. […] The damaged gene, ABCD1, that causes ALD resides on the X chromosome. Boys inherit only one X chromosome, which is passed to them from their mothers. Girls inherit two X chromosomes, one from each parent. Girls typically inherit one functional ABCD1 gene from their unaffected parent, which usually protects female children from the disease, but is not enough to protect women from developing symptoms as they age. […] Yes, ALD is caused by a genetic mutation, so it often runs in families.

• #32 Adrenoleukodystrophy – United Leukodystrophy Foundation

  https://ulf.org/leukodystrophies/adrenoleukodystrophy/

  The peroxisome is a cellular compartment that is responsible for the breakdown of certain types of fatty acids (very long chain fatty acids). In X-ALD, this ability is impaired, resulting in the accumulation of very long chain fatty acids. This leads to the breakdown of the myelin sheath, resulting in the neurologic problems characteristic of leukodystrophies. […] The gene that is defective in X-ALD is called ABCD1, and encodes a protein called ALDP (which stands for ALD protein). This protein resides in the wall of the peroxisome, and is involved in the breakdown of fatty acids. However, its exact role in this process is currently unclear. […] It is worth noting that the specific mutation present in the ALD gene does not necessarily predict the course of the disease. Practically, this means that the fact that two members of a single family harbor the same mutation does NOT mean that the clinical course of the disease will be identical. […] As we mentioned before, the gene responsible for X-ALD is present on the X chromosome, which leads to the X-linked inheritance pattern seen in this disease.

• #33 X-linked adrenoleukodystrophy (X-ALD): clinical presentation and guidelines for diagnosis, follow-up and management | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-7-51

  The VLCFA homeostasis in X-ALD is disturbed. This may contribute to the destabilization of the myelin sheath and impair the function of astrocytes and microglia which play an important role in myelin integrity. […] Not all males with X-ALD develop cerebral ALD corroborating the notion that additional triggers, genetic, epigenetic and/or environmental, modify this process. […] In the absence of a relevant X-ALD mouse model that develops cerebral demyelination with neuroinflammation, the pathogenic processes that result in cerebral demyelination and subsequently severe neuroinflammation remains therefore poorly understood.

• #34 Adrenoleukodystrophy – Wikipedia

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

  Adrenoleukodystrophy (ALD) is a disease linked to the X chromosome. It is a result of fatty acid buildup caused by failure of peroxisomal fatty acid beta oxidation which results in the accumulation of very long chain fatty acids in tissues throughout the body. […] ALD is caused by mutations in ABCD1, a gene located on the X chromosome that codes for ALD, a peroxisomal membrane transporter protein. The exact mechanism of the pathogenesis of the various forms of ALD is not known. […] The exact cause for the varied collection of symptoms found in the different ALD phenotypes is not clear. […] The lack of Coenzyme A does not permit the disintegration of the VLCFA, accumulating the same in the white matter, adrenal glands, and the testes more specifically in the Leydig cells not allowing the proper function of these organs. […] Several studies link inflammation from viral infection or head trauma to development or worsening of symptoms.

• #35

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6031365/

  Indeed, our data indicate that a diet high in medium-chain FAs provides a potential therapeutic approach for leukodystrophy patients with ACS mutations. […] Our finding that environmental stress in the form of light modifies neurodegenerative phenotypes in bgm and dbb models of neurodegeneration provides direct evidence for a gene-environment interaction that modulates penetrance and expressivity of neurodegenerative phenotypes. […] Together, data from these complementary studies identify product loss as causative of neurodegenerative disease. […] Our studies contribute to the fields of ALD and neurodegenerative disease in three major ways: (1) we show that activated VLCFAs and/or their products are necessary for neuronal health and maintenance; (2) we identify new candidate ALD-disease-causing genes, and (3) we show that a diet high in medium-chain FAs shows promise as a potential therapeutic approach for patients with neurometabolic degenerative disease.

• #36 Adrenoleukodystrophy

  https://www.brainfacts.org/diseases-and-disorders/neurological-disorders-az/diseases-a-to-z-from-ninds/adrenoleukodystrophy

  X-linked Adrenoleukodystrophy (ALD) is one of a group of genetic disorders called the leukodystrophies that cause damage to the myelin sheath, an insulating membrane that surrounds nerve cells in the brain. […] People with X-ALD accumulate high levels of saturated, very long chain fatty acids (VLCFA) in the brain and adrenal cortex. […] The loss of myelin and the progressive dysfunction of the adrenal gland are the primary characteristics of X-ALD. […] Almost half the women who are carriers of X-ALS will develop a milder form of AMN but almost never will develop symptoms seen in boys the X-ALD. […] X-ALD should not be confused with neonatal adrenoleukodsystrophy, which is a disease of newborns and young infants and belongs to the group of peroxisomal biogenesis disorders.

• #37

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6031365/

  It is also clear that our current understanding of ALD disease etiology is insufficient for the design of effective treatment protocols; in this regard, therapeutic manipulation of VLCFA levels does not impact disease progression. […] Our demonstration that mutations in long- and medium-chain FA metabolic pathways in Drosophila yield shared loss-of-function neurodegenerative phenotypes extends a single-gene association (ABCD1) for ALD to a pathway association (lipid metabolism). […] Importantly, this more expansive view of ALD offers a possibility of diagnosis to some of the 50% of leukodystrophy patients with undiagnosed conditions. […] Our demonstration that neurodegeneration in fly models of ALD does not result from a buildup of FA precursors, but instead is caused by a lack of activated FA product, shifts our understanding of ALD etiology and is expected to have profound effects on the design of effective therapeutics.

• #38 Reactome | Defective ABCD1 causes ALD

  https://reactome.org/content/detail/R-HSA-5684045

  Defective ABCD1 causes ALD. […] Mutations in the ALD gene result in the X-linked neurodegenerative disorder adrenoleukodystrophy (ALD; MIM:300100). […] ABCD1 deficiency impairs the peroxisomal beta-oxidation of very long-chain fatty acids (VLCFA) and facilitates their further chain elongation by ELOVL1 resulting in accumulation of VLCFA in plasma and tissues. […] In addition to ABCD1, other genes and environmental factors determine clinical features of ALD (Kemp et al. 2012, Berger et al. 2014).

• #39 Adrenoleukodystrophy- Symptoms, Diagnosis, Treatment, & More

  https://www.impactguru.com/info/adrenoleukodystrophy/

  Because the ABCD1 gene is located on the X chromosome, ALD follows an X-linked inheritance pattern. […] Mutations in the ABCD1 gene can be of various types, including point mutations, deletions, or insertions. […] The absence or dysfunction of the ALDP protein disrupts the normal transport of VLCFAs into peroxisomes, accumulating these fatty acids in various tissues. […] Due to the faulty transport of VLCFAs into peroxisomes, these fatty acids build up in the cells. […] The accumulation primarily affects the nervous system and the adrenal glands. […] In addition to neurological symptoms, ALD can also affect the adrenal glands, which produce hormones like cortisol and aldosterone.

• #40 Pediatric adrenoleukodystrophy (ALD) – Children’s Health Endocrinology

  https://www.childrens.com/specialties-services/conditions/adrenoleukodystrophy

  Adrenoleukodystrophy is caused by a gene mutation on the X chromosome, which is passed on from a mother to her child. The condition is more common in males. […] Adrenoleukodystrophy (ALD), also known as X-linked adrenoleukodystrophy (X-ALD), is a rare, genetic disorder in which the body cannot break down fatty acids in the brain. The resulting buildup of fatty acids leads to a breakdown of the myelin sheath the insulation covering that protects the nerve fibers in the brain. This makes it impossible for nerves in the body to communicate with the brain. ALD also affects the adrenal gland, which produces important hormones that control metabolism, blood pressure and the bodys responses to stress.

• #41 Adrenoleukodystrophy: Case Report and Aspects Relevant to the Otorhinolaryngologist

  http://www.arquivosdeorl.org.br/conteudo/acervo_eng.asp?id=637

  The defective gene is responsible for the encoding of an enzyme called fatty acyl CoA ligase that is found in the peroxyssomes membrane and is related to the transport of fatty acids into this cellular structure. […] The precise mechanisms by means of which the VLCFAs cause a destruction in the myelin sheath are still unknown. […] There is no defined therapy for ALD so far, and according to studies, the VLCFA-free diet, such as spinach, cheese and red meat, associated to olive oil or „Lorenzo’s oil” has been successful specially when managed in the beginning or before the appearing of the symptoms. […] The treatment of adrenal disorder, through the administration of hormones and currently the marrow transplants are treatment modalities adopted in the ALD with a very variable level of success in the disease evolution, according to the literature.

• #42

  https://journals.lww.com/md-journal/fulltext/2024/04190/a_novel_abcd1_gene_mutation_causes.46.aspx

  This novel mutation sites filled gaps in the map of pathogenic mutations in the ABCD1 gene, and phenotypic presentation associated with the novel mutation described here was compared to phenotypes linked to other reported mutations occurring at adjacent sites. […] While ABCD1 mutations are implicated, additional genetic and non-genetic factors such as trauma, epigenetic modifications, and environmental exposures may contribute to or modify disease onset and progression. […] The symptoms of AMN predominantly involve the nervous system and can include slowly progressive spastic paraparesis, sensory ataxia, and dysfunctions of the bowel and bladder, occasionally accompanied by fecal incontinence. […] This case expands the known mutation spectrum of ABCD1-linked X-ALD, providing insight into potential genotype-phenotype correlations.

• #43 Adrenoleukodystrophy – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/adrenoleukodystrophy/diagnosis-treatment/drc-20369160

  Blood testing. These tests check for high levels of very long-chain fatty acids (VLCFAs) in your blood, which are a key indicator of adrenoleukodystrophy. […] Doctors use blood samples for genetic testing to identify defects or mutations that cause ALD. […] Adrenoleukodystrophy has no cure. However, stem cell transplantation may stop the progression of ALD if done when neurological symptoms first appear. […] Stem cell transplant. This may be an option to slow or halt the progression of adrenoleukodystrophy in children if ALD is diagnosed and treated early. […] In a recent clinical trial, boys with early-stage cerebral ALD were treated with gene therapy as an alternative to stem cell transplantation. Early results from gene therapy are promising. Disease progression stabilized in 88 percent of boys who participated in the trial. Additional research is necessary to assess long-term results and safety of gene therapy for cerebral ALD.

• #44 Adrenoleukodystrophy and Adrenomyeloneuropathy – Stanford Medicine Children’s Health

  https://www.stanfordchildrens.org/en/services/neuro-immunology/ald.html

  X-linked ALD occurs when myelin, the fatty protective substance that surrounds nerve cells, breaks down. It is the result of a mutation of a specific gene, ABCD1. […] The earliest symptoms include problems with the adrenal glands and behavioral issues, and the disease usually progresses quickly to include vision and hearing loss, seizures, coordination problems, and difficulty swallowing. […] Gene therapy for CALD, which was approved by the U.S. Food and Drug Administration in 2022, is designed to replace the defective or missing ABCD1 gene, which controls the production of an enzyme that our body normally uses to break down fatty acids. […] Stanford experts helped conduct clinical trials for the new therapy, which gives kids with ALD a functioning copy of the abnormal gene that causes the disease.

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