IEMbase 0027: CBS-related cystathionine beta-synthase deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 27 |
| Nosology | 1.5.06.01 |
| Gene | CBS |
| External IDs | OMIM:236200 |
| Generated mapping | MAPPED by alias_exact:classical homocystinuria |
| Candidate DisMech targets | Homocystinuria.yaml |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents classical homocystinuria due to CBS deficiency. The characteristic phenotype set is ectopia lentis, intellectual disability, osteoporosis, thromboembolism, and thromboses/infarcts. Additional features include arachnodactyly, developmental delay, genu valgum, iridodonesis, kyphosis, malar flush, marfanoid habitus, myopia, pes cavus, psychiatric disturbance, scoliosis, seizures, sternal deformities, and stroke.
The biochemical profile is high plasma and urinary homocysteine, high total plasma homocysteine, low-to-normal cystathionine, low cysteine/cystine, variable high methionine, abnormal methionine/cystathionine and methionine/total-homocysteine ratios, urinary nitroprusside positivity, and elevated SAM/SAH markers. Treatments include pyridoxine, betaine, methionine restriction, and a protein-defined diet.
DisMech phenotype coverage
The generated mapping to Homocystinuria.yaml is correct. DisMech covers the
core ocular, vascular, skeletal, neurologic, psychiatric, and biochemical
phenotype in detail: ectopia lentis, myopia, thromboembolism, arterial/venous
thrombosis, pulmonary embolism, cerebral ischemia, intellectual disability,
seizures, osteoporosis, marfanoid habitus, arachnodactyly, scoliosis, pectus
deformities, genu valgum, pes cavus, hypertension, ocular complications, mood
and psychotic symptoms, pancreatitis, hepatomegaly, hyperhomocystinemia,
methionine, cysteine, and several mechanistic biomarkers. Treatments include
pyridoxine, methionine-restricted diet, betaine, folate/B12 supplementation,
thrombosis prevention, supportive care, genetic counseling, and investigational
enzyme replacement therapy.
Concordance and completeness
Judgement: correct mapping and high concordance. DisMech is broader and more mechanistic; IEMbase is useful for several curation gap checks.
IEMbase adds iridodonesis, malar flush, sternal deformities as a broad phrase, urinary nitroprusside testing, DBS methionine-to-phenylalanine ratio, and several sulfur-amino-acid ratio markers. DisMech adds more granular thrombotic phenotypes, ocular complications, treatment nuance, and mechanistic framing around endothelial dysfunction, collagen cross-linking, oxidative stress, protein misfolding, and neuroexcitotoxicity.
Curation actions
- Keep the generated mapping.
- Consider adding iridodonesis and malar flush if evidence supports them.
- Consider whether the IEMbase biochemical ratios or nitroprusside test add useful diagnostic-marker coverage beyond the current homocysteine/methionine markers.