Adrenoleukodystrophy (ALD)

External Ids:

Disease Ontology 12 DOID:10588 OMIM 56 300100 KEGG 36 H00176 ICD9CM 34 341.1 MeSH 43 D000326 D002549 NCIt 49 C61252 C84670 SNOMED-CT 67 49692006 65389002 ICD10 32 E71.52 G37.0

MESH via Orphanet 44 D000326 ICD10 via Orphanet 33 E71.3 UMLS via Orphanet 72 C0162309 C1527231 Orphanet 58 ORPHA139396 ORPHA139399 ORPHA43 MedGen 41 C0162309 C1527231 C2931920 SNOMED-CT via HPO 68 103276001 111563005 12184005 127377003 128613002 15188001 165232002 1845001 192967009 20022000 22325002 228156007 237785004 246545002 247578003 247977003 248004009 248099006 24982008 249945007 250067008 25064002 252157006 255314001 271719001 278040002 281016006 289195008 302226006 302289002 313307000 343087000 363732003 373662000 386584007 397732007 397803000 397974008 398026008 398064005 398432008 406506008 42345000 42658009 44695005 48130008 4830009 49765009 52448006 56317004 59073000 61372001 65956007 69322001 7006003 72042002 7461003 7973008 84757009 87486003 91138005 91175000 95828007 more UMLS 71 C0004712 C0007795 C0036421 C0162309 C1527231 more

Genetics Home Reference : ²⁵ X-linked adrenoleukodystrophy is a genetic disorder that occurs primarily in males. It mainly affects the nervous system and the adrenal glands, which are small glands located on top of each kidney. In this disorder, the fatty covering (myelin) that insulates nerves in the brain and spinal cord is prone to deterioration (demyelination), which reduces the ability of the nerves to relay information to the brain. In addition, damage to the outer layer of the adrenal glands (adrenal cortex) causes a shortage of certain hormones (adrenocortical insufficiency). Adrenocortical insufficiency may cause weakness, weight loss, skin changes, vomiting, and coma. There are three distinct types of X-linked adrenoleukodystrophy: a childhood cerebral form, an adrenomyeloneuropathy type, and a form called Addison disease only. Children with the cerebral form of X-linked adrenoleukodystrophy experience learning and behavioral problems that usually begin between the ages of 4 and 10. Over time the symptoms worsen, and these children may have difficulty reading, writing, understanding speech, and comprehending written material. Additional signs and symptoms of the cerebral form include aggressive behavior, vision problems, difficulty swallowing, poor coordination, and impaired adrenal gland function. The rate at which this disorder progresses is variable but can be extremely rapid, often leading to total disability within a few years. The life expectancy of individuals with this type depends on the severity of the signs and symptoms and how quickly the disorder progresses. Individuals with the cerebral form of X-linked adrenoleukodystrophy usually survive only a few years after symptoms begin but may survive longer with intensive medical support. Signs and symptoms of the adrenomyeloneuropathy type appear between early adulthood and middle age. Affected individuals develop progressive stiffness and weakness in their legs (paraparesis), experience urinary and genital tract disorders, and often show changes in behavior and thinking ability. Most people with the adrenomyeloneuropathy type also have adrenocortical insufficiency. In some severely affected individuals, damage to the brain and nervous system can lead to early death. People with X-linked adrenoleukodystrophy whose only symptom is adrenocortical insufficiency are said to have the Addison disease only form. In these individuals, adrenocortical insufficiency can begin anytime between childhood and adulthood. However, most affected individuals develop the additional features of the adrenomyeloneuropathy type by the time they reach middle age. The life expectancy of individuals with this form depends on the severity of the signs and symptoms, but typically this is the mildest of the three types. Rarely, individuals with X-linked adrenoleukodystrophy develop multiple features of the disorder in adolescence or early adulthood. In addition to adrenocortical insufficiency, these individuals usually have psychiatric disorders and a loss of intellectual function (dementia). It is unclear whether these individuals have a distinct form of the condition or a variation of one of the previously described types. For reasons that are unclear, different forms of X-linked adrenoleukodystrophy can be seen in affected individuals within the same family.

MalaCards based summary : Adrenoleukodystrophy, also known as x-linked adrenoleukodystrophy, is related to adrenomyeloneuropathy and neonatal adrenoleukodystrophy, and has symptoms including seizures, ataxia and pruritus. An important gene associated with Adrenoleukodystrophy is ABCD1 (ATP Binding Cassette Subfamily D Member 1), and among its related pathways/superpathways are ABC transporters and Peroxisome. The drugs Tadalafil and Bosentan have been mentioned in the context of this disorder. Affiliated tissues include skin, brain and lung, and related phenotypes are intellectual disability and gait disturbance

Disease Ontology : ¹² A leukodystrophy that disrupts the breakdown of very-long-chain fatty acids resulting in progressive brain damage, failure of the adrenal glands and eventually death.

NIH Rare Diseases : ⁵² X-linked adrenoleukodystrophy (X-ALD) is a genetic disease that affects the nervous system and the adrenal glands (small glands located on top of each kidney). People with this disease often have progressive loss of the fatty covering (myelin ) that surrounds the nerves in the brain and spinal cord. They may also have a shortage of certain hormones that is caused by damage to the outer layer of the adrenal glands (adrenal cortex). This is called adrenocortical insufficiency , or Addison disease. There are three forms of X-ALD: a childhood cerebral form , an adrenomyeloneuropathy (AMN) type, and an adrenal-insufficiency-only-type. The disease primarily affects males. X-ALD is caused by a variation (mutation ) in the ABCD1 gene and it is inherited in an X-linked. manner . Diagnosis of the disease is based on testing the levels of a molecule called very long-chain fatty acids (VLCFA). The diagnosis can be confirmed with genetic testing . There is still no cure for X-ALD, but taking special oils such as Lorenzo's oil can lower the blood levels of VLCFA. Bone marrow transplantation may be an option for boys who have evidence of brain involvement on MRI , but do not yet have obvious symptoms of the disease with a normal neurological exam. Adrenocortical insufficiency is treated with corticosteroids .

OMIM : ⁵⁶ Adrenoleukodystrophy is an X-linked disorder which is secondary to a mutation in the ABCD1 gene and results in the apparent defect in peroxisomal beta oxidation and the accumulation of the saturated very long chain fatty acids (VLCFA) in all tissues of the body. The manifestations of the disorder occur primarily in the adrenal cortex, the myelin of the central nervous system, and the Leydig cells of the testes. ABCD1 is an ATPase binding cassette protein in the same category of transporter proteins such as the CFTR and MDR proteins. Identification of X-ALD as a lipid-storage disease, as a defect in the capacity to degrade VLCFAs, and its characterization as a peroxisomal disorder was reviewed by Moser (1997). Moser et al. (2005) provided a clinical review of ALD. (300100)

NINDS : ⁵³ 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. Women have two X chromosomes and are the carriers of the disease, but since men only have one X chromosome and lack the protective effect of the extra X chromosome, they are more severely affected.  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. While nearly all patients with X-ALD suffer from adrenal insufficiency, also known as Addison's disease, the neurological symptoms can begin either in childhood or in adulthood. The childhood cerebral form is the most severe, with onset between ages 4 and 10. The most common symptoms are usually behavioral changes such as abnormal withdrawal or aggression, poor memory, and poor school performance. Other symptoms include visual loss, learning disabilities, seizures, poorly articulated speech, difficulty swallowing, deafness, disturbances of gait and coordination, fatigue, intermittent vomiting, increased skin pigmentation, and progressive dementia. The milder adult-onset form is also known as adrenomyeloneuropathy (AMN), which typically begins between ages 21 and 35.  Symptoms may include progressive stiffness, weakness or paralysis of the lower limbs, and ataxia. Although adult-onset ALD progresses more slowly than the classic childhood form, it can also result in deterioration of brain function. Almost half the women who are carriers of X-ALS will develop a milder form of AMN; such carriers almost never develop symptoms that are 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.

KEGG : ³⁶ Adrenoleukodystrophy (ALD) is an X-linked disorder caused by mutation in the ABCD1 gene that encodes ABCD1/ALDP, a peroxisomal ABC transporter. ALD is biochemically characterized by the accumulation of saturated very long chain fatty acids (VLCFA) in tissues such as adrenal cortex and white matter of central nervous system. The phenotypes can be subdivided into four main categories: Childhood cerebral adrenoleukodystrophy (CCER), adrenomyeloneuropathy (AMN), Addison-only, and asymptomatic. This disorder is characterized by progressive behavioral, cognitive and neurologic deficit.

UniProtKB/Swiss-Prot : ⁷³ Adrenoleukodystrophy: A peroxisomal metabolic disorder characterized by progressive multifocal demyelination of the central nervous system and by peripheral adrenal insufficiency (Addison disease). It results in mental deterioration, corticospinal tract dysfunction, and cortical blindness. Different clinical manifestations exist like: cerebral childhood ALD (CALD), adult cerebral ALD (ACALD), adrenomyeloneuropathy (AMN) and 'Addison disease only' (ADO) phenotype.

Wikipedia : ⁷⁴ Adrenoleukodystrophy (ALD) is a disease linked to the X chromosome. It is a result of fatty acid buildup... more...

GeneReviews: NBK1315

Clinical features from OMIM:

300100

#	Description	GenomeRNAi Source Accession	Score	Top Affiliating Genes
1	Decreased viability	GR00221-A-1	9.58	PPARA
2	Decreased viability	GR00221-A-2	9.58	PPARA
3	Decreased viability	GR00221-A-3	9.58	PPARA
4	Decreased viability	GR00221-A-4	9.58	PPARA
5	Decreased viability	GR00240-S-1	9.58	PEX26
6	Decreased viability	GR00249-S	9.58	ACOX1 SLC25A17
7	Decreased viability	GR00301-A	9.58	PPARA
8	Decreased viability	GR00381-A-1	9.58	PPARA
9	Decreased viability	GR00386-A-1	9.58	MOG PEX19 PEX26 SLC25A17 SLC27A2
10	Decreased viability	GR00402-S-2	9.58	ABCD1 ABCD3 PEX10 PEX26

Search NIH Clinical Center for Adrenoleukodystrophy

Chloroquine Chloroquine hydrochloride chloroquine phosphate Epoprostenol

Epoprostenol Sodium Potassium aminobenzoate Tolazoline Tolazoline Hydrochloride