IEMbase 0296: GLA-related Alpha-galactosidase A deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 296 |
| Nosology | 20.1.13.01 |
| Gene | GLA |
| External IDs | OMIM:301500; ORPHA:324 |
| Generated mapping | MAPPED; Fabry_Disease.yaml |
| Candidate DisMech targets | Fabry_Disease.yaml |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents Fabry disease / alpha-galactosidase A deficiency. Inheritance is marked X-linked, treatability is yes, and prevalence is listed as 1:40,000.
Clinical rows include the core Fabry pattern: angiokeratoma, cornea verticillata, sensorineural hearing loss, proteinuria, stroke-like encephalopathy, abdominal pain, hypertrophic cardiomyopathy, cerebral infarction, neuropathic pain, chronic renal failure, and upper-airway or airway obstruction. IEMbase also adds coarser review prompts such as pulmonary fibrosis, malignant neoplasia, thyroid dysfunction, coarse facial features, bulbous/prominent nose, thick eyebrows, thick lips, recessed forehead, and an ear-lobule dysmorphism row with a source spelling typo. Biochemical rows show increased globotriaosylceramide and globotriaosylsphingosine. Treatment rows list agalsidase alfa, agalsidase beta, and migalastat.
DisMech phenotype coverage
Fabry_Disease.yaml is the correct local target. It models GLA deficiency,
lysosomal Gb3 and lyso-Gb3 accumulation, tissue-specific renal, cardiac,
vascular, autonomic, peripheral nerve, ocular, and cutaneous storage, and
classic and late-onset cardiac subtypes.
Local phenotype coverage is broad: acroparesthesia, neuropathic pain, hypohidrosis, heat intolerance, abdominal pain, nausea/vomiting, angiokeratoma, proteinuria, chronic kidney disease, left ventricular hypertrophy, arrhythmia, stroke, transient ischemic attack, hearing impairment, tinnitus, cornea verticillata, cataract, elevated Gb3, reduced alpha-galactosidase A activity, nephrotic syndrome, heart failure, and conjunctival telangiectasia. Treatment coverage includes enzyme replacement therapy, pharmacological chaperone therapy, investigational substrate reduction, gene therapy, and supportive care.
Concordance and completeness
Judgement: correct high-concordance mapping to Fabry_Disease.yaml.
IEMbase and DisMech agree on GLA identity, X-linked inheritance, Gb3/lyso-Gb3 storage, renal disease, hypertrophic cardiomyopathy, cerebrovascular disease, neuropathic pain, angiokeratoma, cornea verticillata, hearing involvement, and the ERT/chaperone treatment landscape. DisMech is substantially richer for mechanism, subtype structure, renal/cardiac/autonomic pathophysiology, and therapy classes.
IEMbase adds specific review prompts for airway obstruction, pulmonary fibrosis, malignancy, thyroid dysfunction, and dysmorphic facial/ear rows. These should be handled cautiously before import because some may be nonspecific, secondary, or rare rather than core Fabry features.
Curation actions
- Keep this record mapped to
Fabry_Disease.yaml. - Use the IEMbase treatment rows to check whether local ERT/chaperone entries should explicitly name agalsidase alfa, agalsidase beta, and migalastat.
- Review the IEMbase airway, pulmonary fibrosis, malignancy, thyroid, and dysmorphic rows before adding them locally.