IEMbase 0094: HLCS-related holocarboxylase synthetase deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 94 |
| Nosology | 21.7.02.01 |
| Gene | HLCS |
| External IDs | OMIM:253270 |
| Generated mapping | MAPPED to Holocarboxylase_Synthetase_Deficiency.yaml |
| Candidate DisMech targets | Holocarboxylase_Synthetase_Deficiency.yaml |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents this as autosomal recessive HLCS-related holocarboxylase synthetase deficiency, with alternate labels infantile-onset multiple carboxylase deficiency and HCSD. Treatability is marked yes.
The characteristic biochemical rows are urinary 3-methylcrotonylglycine, C5-OH acylcarnitine in dried blood spot or plasma, urinary 3-hydroxypropionic acid, and plasma lactate. Urinary methylcitric acid is also present in the wider panel.
The characteristic clinical rows are alopecia, ataxia, skin rash, and mitral valvulitis.
Treatment is biotin.
DisMech phenotype coverage
The generated mapping is correct. Holocarboxylase_Synthetase_Deficiency.yaml
directly models HLCS deficiency as impaired protein biotinylation and
functional deficiency of the biotin-dependent carboxylases.
DisMech covers the major biochemical and clinical signals: C5-OH, lactate, 3-hydroxyisovaleric acid, 3-methylcrotonylglycine, 3-hydroxypropionate, methylcitric acid, skin rash, alopecia, seizures, hypotonia, developmental delay, feeding/growth problems, metabolic acidosis, hyperammonemia, and biotin supplementation. It also models neonatal and late-onset presentations, biotin responsiveness, newborn-screening issues, and genotype-response detail.
Concordance and completeness
Judgement: high concordance.
IEMbase adds ataxia and mitral valvulitis as characteristic clinical rows. DisMech is stronger for mechanism, multi-carboxylase branch logic, acute decompensation detail, and biotin treatment response.
Curation actions
- Keep the generated mapping to
Holocarboxylase_Synthetase_Deficiency.yaml. - Consider reviewing ataxia and mitral valvulitis for possible phenotype additions if source evidence supports them.
- Preserve dried-blood-spot versus plasma C5-OH distinctions if lab compartment granularity is added later.