MCID: CHL077
MIFTS: 14

Childhood-Onset Cerebral X-Linked Adrenoleukodystrophy

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

Aliases & Classifications for Childhood-Onset Cerebral X-Linked Adrenoleukodystrophy

MalaCards integrated aliases for Childhood-Onset Cerebral X-Linked Adrenoleukodystrophy:

Name: Childhood-Onset Cerebral X-Linked Adrenoleukodystrophy 38 53 29
Adrenoleukodystrophy Childhood Cerebral Form 53
Adrenoleukodystrophy X-Linked Cerebral Form 53
Ald Childhood Cerebral Form 53
Childhood Cerebral Ald 53

Classifications:



Summaries for Childhood-Onset Cerebral X-Linked Adrenoleukodystrophy

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 139396Disease definitionX-linked cerebral adrenoleukodystrophy (X-CALD), a subtype of X-linked adrenoleukodystrophy (X-ALD, see this term), is a peroxisomal disease characterized by severe inflammatory demyelination in the brain, and often associated with adrenal insufficiency.EpidemiologyX-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 descriptionX-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 insufficiency (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 deficits such as hemiplegia or quadriparesis, cerebellar ataxia, impaired central auditory discrimination, visual field 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.EtiologyX-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 methodsGenetic 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 diagnosisInitial symptoms in boys may ressemble ADD. AI symptoms may resemble congenital or acquired forms of Addison disease (see this term).Antenatal diagnosisGestational chorionic villus sampling (10-13 weeks), amniocentesis (15-18 weeks) and pre-implantation genetic testing are feasibleGenetic counselingTransmission is X-linked, with less than 8% de novo 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 treatmentBrain 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.PrognosisLeft 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.Visit the Orphanet disease page for more resources.

MalaCards based summary : Childhood-Onset Cerebral X-Linked Adrenoleukodystrophy, also known as adrenoleukodystrophy childhood cerebral form, is related to adrenoleukodystrophy. Affiliated tissues include testes, brain and bone.

Related Diseases for Childhood-Onset Cerebral X-Linked Adrenoleukodystrophy

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

# Related Disease Score Top Affiliating Genes
1 adrenoleukodystrophy 10.4

Symptoms & Phenotypes for Childhood-Onset Cerebral X-Linked Adrenoleukodystrophy

Drugs & Therapeutics for Childhood-Onset Cerebral X-Linked Adrenoleukodystrophy

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Early Diagnosis Of Childhood Cerebral ALD Withdrawn NCT02948062

Search NIH Clinical Center for Childhood-Onset Cerebral X-Linked Adrenoleukodystrophy

Cell-based therapeutics:


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

Genetic Tests for Childhood-Onset Cerebral X-Linked Adrenoleukodystrophy

Genetic tests related to Childhood-Onset Cerebral X-Linked Adrenoleukodystrophy:

# Genetic test Affiliating Genes
1 Childhood-Onset Cerebral X-Linked Adrenoleukodystrophy 29

Anatomical Context for Childhood-Onset Cerebral X-Linked Adrenoleukodystrophy

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

41
Testes, Brain, Bone, Bone Marrow

Publications for Childhood-Onset Cerebral X-Linked Adrenoleukodystrophy

Articles related to Childhood-Onset Cerebral X-Linked Adrenoleukodystrophy:

# Title Authors Year
1
Childhood-onset cerebral X-linked adrenoleukodystrophy. ( 11075798 )
2000
2
Long-term effect of bone-marrow transplantation for childhood-onset cerebral X-linked adrenoleukodystrophy. ( 11085690 )
2000

Variations for Childhood-Onset Cerebral X-Linked Adrenoleukodystrophy

Expression for Childhood-Onset Cerebral X-Linked Adrenoleukodystrophy

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

Pathways for Childhood-Onset Cerebral X-Linked Adrenoleukodystrophy

GO Terms for Childhood-Onset Cerebral X-Linked Adrenoleukodystrophy

Sources for Childhood-Onset Cerebral X-Linked Adrenoleukodystrophy

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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