IEMbase 0280: ABCD1-related X-linked adrenoleukodystrophy and adrenomyeloneuropathy
Scope
| Field | Value |
|---|---|
| IEMbase ID | 280 |
| Nosology | 14.2.01.01 |
| Gene | ABCD1 |
| External IDs | OMIM:300100; ORPHA:369942 |
| Generated mapping | UNMAPPED; weak candidate adrenoleukodystrophy.yaml |
| Candidate DisMech targets | adrenoleukodystrophy.yaml |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents ABCD1-related X-linked adrenoleukodystrophy and adrenomyeloneuropathy. Prevalence is listed as 1:17,000. Treatability is marked yes.
The characteristic clinical row is hyperpigmentation. Additional rows include adrenal insufficiency, Addison crisis, electrolyte changes, gonadal failure, sexual dysfunction, leukodystrophy, spastic paresis, peripheral nerve involvement, sphincter-control problems, behavioral disorder, dementia, epilepsy, abnormal EEG, abnormal brain evoked response audiometry, abnormal VEP, perceptive hearing loss, vision loss or optic atrophy, and alopecia. The biochemical hallmark is increased plasma very-long-chain fatty acids.
Treatment rows include hematopoietic stem-cell transplant, marked as lowering VLCFA and targeting neurologic features, and lentiviral gene therapy for cerebral adrenoleukodystrophy.
DisMech phenotype coverage
adrenoleukodystrophy.yaml is the correct local target despite the generated
UNMAPPED status. The local entry models ABCD1-mediated peroxisomal fatty-acid
transport failure, VLCFA accumulation, oxidative stress, astrocyte and
microglial dysfunction, blood-brain-barrier disruption, inflammatory cerebral
demyelination, adrenomyeloneuropathy spinal-cord axonopathy, adrenocortical
dysfunction, and gonadal dysfunction. It includes childhood cerebral ALD, AMN,
and Addison-only subtypes.
The local phenotype coverage includes progressive spastic paraplegia, bladder and bowel dysfunction, adrenal insufficiency, hyperpigmentation, weight loss, anorexia, CNS demyelination, cerebral white-matter lesions, hypogonadism, leukoencephalopathy, behavioral abnormality, cognitive impairment, visual loss, progressive myelopathy, and peripheral neuropathy. Local treatments include lentiviral gene therapy, hematopoietic stem-cell transplantation, glucocorticoid replacement, VLCFA testing, molecular testing, and brain MRI.
Concordance and completeness
Judgement: false negative mapping; resolve to adrenoleukodystrophy.yaml.
IEMbase and DisMech agree on ABCD1 identity, X-linked inheritance, elevated plasma VLCFA, adrenal disease with hyperpigmentation, cerebral leukodystrophy, AMN/spastic myelopathy, peripheral nerve involvement, sphincter dysfunction, gonadal/sexual dysfunction, behavioral and cognitive disease, visual involvement, HSCT, and lentiviral gene therapy. DisMech is richer for mechanistic chain, subtype structure, adrenal steroid replacement, diagnostics, and current trial context.
IEMbase adds review prompts for perceptive hearing loss, abnormal BAEP/VEP, EEG abnormality, alopecia, and Addison-crisis wording.
Curation actions
- Resolve this record to
adrenoleukodystrophy.yaml. - Treat the generated weak candidate as a true target; the low score appears to be a matching/naming artifact rather than a biology issue.
- Use IEMbase's hearing-test, VEP/EEG, alopecia, and Addison-crisis rows as enrichment prompts.