MCID: XLN182
MIFTS: 22

X-Linked Cerebral Adrenoleukodystrophy

Categories: Blood diseases, Endocrine diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for X-Linked Cerebral Adrenoleukodystrophy

MalaCards integrated aliases for X-Linked Cerebral Adrenoleukodystrophy:

Name: X-Linked Cerebral Adrenoleukodystrophy 20 6 37
Adrenoleukodystrophy Childhood Cerebral Form 20
Adrenoleukodystrophy X-Linked Cerebral Form 20
Ald Childhood Cerebral Form 20
Childhood Cerebral Ald 20
X-Cald 20

Classifications:



Summaries for X-Linked Cerebral Adrenoleukodystrophy

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 139396 Definition A subtype of X-linked adrenoleukodystrophy (X-ALD), a peroxisomal disease characterized by severe inflammatory demyelination in the brain, and often associated with adrenal insufficiency. Epidemiology X-CALD manifests in 70% of male and 2% of female cases of X-ALD, whose estimated birth incidence (male and female) is 1/20,000. Clinical description X-CALD may occur in healthy boys (2.5-10 years old, 50% of cases), in symptomatic male adrenomyeloneuropathy (AMN, see this term) cases (35%), in adult males as the initial manifestation of X-ALD (~12%) and most rarely in adult women (2%). Adrenocortical insuf?ciency (AI, 65% of cases) is often latent, lacking melanoderma, presenting as fatigue, nausea or even acute primary adrenal insufficiency (see this term). AI sometimes precedes neurologic symptoms that are limited to mild cognitive dysfunction mimicking attention deficit disorder (ADD) in children. An active phase follows: emotional lability, cognitive decline and either visuospatial impairment or frontal syndrome are rapidly accompanied by de?cits such as hemiplegia or quadriparesis, cerebellar ataxia, impaired central auditory discrimination, visual ?eld defects, cortical blindness and often seizures. Patients may lose the ability to understand language and to walk within weeks. Some patients (10%) remain in a chronic or arrested X-CALD and often develop marked visual-spatial and cognitive deficits. Disturbances resembling schizophrenia or psychosis may occur, particularly in adolescents and adults. Etiology X-CALD is due to mutations of ABCD1 (Xq28,) encoding ALDP, a peroxisomal transmembrane protein involved in the transport of very long chain fatty acid CoA-esters (VLCFA) into the peroxisome; perturbing VLCFA homeostasis in glial cells contributes to myelin destabilization. This leads to severe neuroinflammation with impairment of the neuro-vascular unit followed by rapid functional decline. Diagnostic methods Genetic testing must be preceded in men by testing for high plasma concentrations of VLCFA. Initially, brain MRI reveals characteristic abnormal white matter signals, often in the splenium or genu of the corpus callosum. Then, the extent of demyelinating lesions progresses, as revealed by peripheral injection of gadolinium. Differential diagnosis Initial symptoms in boys may ressemble ADD. AI symptoms may resemble congenital or acquired forms of Addison disease (see this term). Antenatal diagnosis Gestational chorionic villus sampling (10-13 weeks), amniocentesis (15-18 weeks) and pre-implantation genetic testing are feasible Genetic counseling Transmission is X-linked, with less than 8% de novo <.i> mutations. Genetic testing of parents and male extended family is mandatory to permit early detection by brain MRI and to propose therapeutic intervention. Systematic testing of women at risk to be carriers is also warranted to propose genetic counseling. Management and treatment Brain MRI is the sole means to detect demyelination prior to symptomatic onset and must be performed every 6 months from 3-12 years, and then annually up to 50 years for all X-ALD males. Allogeneic hematopoietic stem cell transplant (HSCT) remains the only therapeutic intervention that can halt cerebral demyelination, but only when performed at a very early stage. Appropriate donors (HLA-identical non-affected siblings, HLA-matched unrelated donors or cord blood) must be identified rapidly. Autologous HSCT, genetically corrected ex vivo, had a similar efficacy to allogeneic HSCT in the first 4 treated patients. AI and hypogonadism are not cured by HSCT. Plasma testosterone, cortisol, mineralocorticoids, ACTH levels and ACTH stimulation reponses must be tested regularly. Replacement therapy may be required. Prognosis Left untreated, all but 10% of patients are bedridden, blind, lacking speech and require fulltime care, dying within 2-5 years. Arrested X-CALD may enter a phase of rapid neurological deterioration at any time.

MalaCards based summary : X-Linked Cerebral Adrenoleukodystrophy, also known as adrenoleukodystrophy childhood cerebral form, is related to adrenoleukodystrophy and adrenomyeloneuropathy. An important gene associated with X-Linked Cerebral Adrenoleukodystrophy is ABCD1 (ATP Binding Cassette Subfamily D Member 1). Affiliated tissues include brain, and related phenotypes are mental deterioration and very long chain fatty acid accumulation

Related Diseases for X-Linked Cerebral Adrenoleukodystrophy

Diseases related to X-Linked Cerebral Adrenoleukodystrophy via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 adrenoleukodystrophy 11.4
2 adrenomyeloneuropathy 10.4
3 neuroleptic malignant syndrome 10.1

Symptoms & Phenotypes for X-Linked Cerebral Adrenoleukodystrophy

Human phenotypes related to X-Linked Cerebral Adrenoleukodystrophy:

31 (show all 39)
# Description HPO Frequency HPO Source Accession
1 mental deterioration 31 hallmark (90%) HP:0001268
2 very long chain fatty acid accumulation 31 hallmark (90%) HP:0008167
3 myelopathy 31 hallmark (90%) HP:0002196
4 decreased circulating cortisol level 31 hallmark (90%) HP:0008163
5 diffuse demyelination of the cerebral white matter 31 hallmark (90%) HP:0007162
6 abnormality of the periventricular white matter 31 frequent (33%) HP:0002518
7 peripheral axonal neuropathy 31 frequent (33%) HP:0003477
8 sensorimotor neuropathy 31 frequent (33%) HP:0007141
9 abnormal circulating fatty-acid concentration 31 frequent (33%) HP:0004359
10 global brain atrophy 31 frequent (33%) HP:0002283
11 abnormality of the brainstem white matter 31 frequent (33%) HP:0012501
12 dysarthria 31 occasional (7.5%) HP:0001260
13 dysphagia 31 occasional (7.5%) HP:0002015
14 hearing impairment 31 occasional (7.5%) HP:0000365
15 dysmetria 31 occasional (7.5%) HP:0001310
16 memory impairment 31 occasional (7.5%) HP:0002354
17 spastic tetraparesis 31 occasional (7.5%) HP:0001285
18 hemiparesis 31 occasional (7.5%) HP:0001269
19 oculomotor apraxia 31 occasional (7.5%) HP:0000657
20 hyperactivity 31 occasional (7.5%) HP:0000752
21 confusion 31 occasional (7.5%) HP:0001289
22 lower limb spasticity 31 occasional (7.5%) HP:0002061
23 male hypogonadism 31 occasional (7.5%) HP:0000026
24 difficulty walking 31 occasional (7.5%) HP:0002355
25 short attention span 31 occasional (7.5%) HP:0000736
26 ankle clonus 31 occasional (7.5%) HP:0011448
27 hamstring contractures 31 occasional (7.5%) HP:0003089
28 generalized hyperreflexia 31 occasional (7.5%) HP:0007034
29 impaired visuospatial constructive cognition 31 occasional (7.5%) HP:0010794
30 limb myoclonus 31 occasional (7.5%) HP:0045084
31 facial myokymia 31 occasional (7.5%) HP:0000317
32 visual agnosia 31 occasional (7.5%) HP:0030222
33 nasogastric tube feeding 31 occasional (7.5%) HP:0040288
34 astereognosia 31 occasional (7.5%) HP:0010527
35 hoffmann sign 31 occasional (7.5%) HP:0031993
36 seizure 31 occasional (7.5%) HP:0001250
37 blindness 31 very rare (1%) HP:0000618
38 inability to walk 31 very rare (1%) HP:0002540
39 vegetative state 31 very rare (1%) HP:0031358

Drugs & Therapeutics for X-Linked Cerebral Adrenoleukodystrophy

Search Clinical Trials , NIH Clinical Center for X-Linked Cerebral Adrenoleukodystrophy

Cell-based therapeutics:


LifeMap Discovery
Data from LifeMap, the Embryonic Development and Stem Cells Database
Stem-cell-based therapeutic approaches for X-Linked Cerebral Adrenoleukodystrophy:
ABCD-1-transduced hematopoietic stem cells for the treatment of childhood cerebral X-linked adrenoleukodystrophy (CCALD)
Embryonic/Adult Cultured Cells Related to X-Linked Cerebral Adrenoleukodystrophy:
ABCD-1-transduced peripheral blood-derived hematopoietic stem cells PMIDs: 19892975

Genetic Tests for X-Linked Cerebral Adrenoleukodystrophy

Anatomical Context for X-Linked Cerebral Adrenoleukodystrophy

MalaCards organs/tissues related to X-Linked Cerebral Adrenoleukodystrophy:

40
Brain

Publications for X-Linked Cerebral Adrenoleukodystrophy

Articles related to X-Linked Cerebral Adrenoleukodystrophy:

# Title Authors PMID Year
1
Quality of life among boys with adrenoleukodystrophy following hematopoietic stem cell transplant. 61
28934891 2018
2
Anaesthesia for a child with adrenoleukodystrophy: A case report and review of the literature. 61
24700903 2014
3
Magnetic resonance spectroscopy changes following haemopoietic stem cell transplantation in children with cerebral adrenoleukodystrophy. 61
17254002 2007
4
Role of leukotrienes as indicators of the inflammatory demyelinating reaction in x-linked cerebral adrenoleukodystrophy. 61
14586618 2003
5
Neuroleptic malignant syndrome during zuclopenthixol therapy in X-linked cerebral adrenoleukodystrophy. 61
11757591 2001
6
Diffusion tensor brain MR imaging in X-linked cerebral adrenoleukodystrophy. 61
11222805 2001
7
Intrathecal IgA synthesis in X-linked cerebral adrenoleukodystrophy. 61
9378899 1997

Variations for X-Linked Cerebral Adrenoleukodystrophy

ClinVar genetic disease variations for X-Linked Cerebral Adrenoleukodystrophy:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ABCD1 NM_000033.4(ABCD1):c.1816T>C (p.Ser606Pro) SNV Uncertain significance 218422 rs201774661 GRCh37: X:153008476-153008476
GRCh38: X:153743022-153743022

Expression for X-Linked Cerebral Adrenoleukodystrophy

Search GEO for disease gene expression data for X-Linked Cerebral Adrenoleukodystrophy.

Pathways for X-Linked Cerebral Adrenoleukodystrophy

GO Terms for X-Linked Cerebral Adrenoleukodystrophy

Sources for X-Linked Cerebral Adrenoleukodystrophy

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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