IEMbase 0286: HEXA-related Beta-hexosaminidase subunit alpha deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 286 |
| Nosology | 20.1.05.01 |
| Gene | HEXA |
| External IDs | OMIM:272800; ORPHA:309192 |
| Generated mapping | MAPPED; Tay-Sachs_Disease.yaml |
| Candidate DisMech targets | Tay-Sachs_Disease.yaml |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents Tay-Sachs disease / GM2 gangliosidosis B variant due to HEXA alpha-subunit deficiency. Inheritance is autosomal recessive, treatability is unknown, and prevalence is listed as 1:320,000 overall and 1:3,900 in Jewish populations.
The clinical rows span the Tay-Sachs age spectrum: ataxia, psychotic behavior, dystonia, hepatosplenomegaly, macrocephaly, psychiatric disturbance, spasticity, and urinary incontinence. Biochemical rows list decreased beta-hexosaminidase A, normal-to-increased beta-hexosaminidase A+B activity, increased urinary oligosaccharides, and increased serum LysoGM2.
DisMech phenotype coverage
Tay-Sachs_Disease.yaml is the correct local target. The entry models HEXA
pathogenic variants, beta-hexosaminidase A deficiency, residual enzyme activity
in late-onset disease, GM2 ganglioside accumulation, neuronal lysosomal storage,
and infantile, juvenile, and late-onset subtypes.
Local phenotypes include developmental regression, cherry-red spot, exaggerated startle response, hypotonia, seizures, macrocephaly, blindness, visual impairment, ataxia, muscle weakness, skeletal muscle atrophy, proximal muscle weakness, psychosis, progressive spasticity, dysarthria, dysphagia, GM2 ganglioside accumulation, hypomyelination, cerebellar atrophy, and tremor. Local biochemical coverage includes hexosaminidase A activity and GM2 ganglioside. Treatments include supportive care, genetic counseling, HSCT context, substrate reduction therapy, pharmacological chaperone therapy, and investigational gene therapy.
Concordance and completeness
Judgement: correct mapping with high phenotype concordance.
IEMbase and DisMech agree on HEXA/Tay-Sachs identity, autosomal recessive inheritance, reduced hexosaminidase A, preserved total A+B activity, GM2 storage logic, ataxia, dystonia/extrapyramidal disease, macrocephaly, psychiatric or psychotic late-onset manifestations, and spasticity. DisMech is broader for subtype structure, neuro-ophthalmic findings, treatment landscape, and mechanism.
IEMbase adds review prompts for urinary incontinence, urinary oligosaccharides, LysoGM2, and hepatosplenomegaly. The hepatosplenomegaly row should be treated cautiously before import, because visceral involvement is more typical of Sandhoff disease and other lysosomal disorders than classic Tay-Sachs.
Curation actions
- Keep this record mapped to
Tay-Sachs_Disease.yaml. - Use IEMbase's LysoGM2 and urinary oligosaccharide rows as biomarker review prompts.
- Review hepatosplenomegaly and urinary incontinence against Tay-Sachs-specific sources before adding them locally.