IEMbase 0176: HMGCS2-related HMG-CoA synthase deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 176 |
| Nosology | 4.3.01.01 |
| Gene | HMGCS2 |
| External IDs | OMIM:605911; ORPHA:35701 |
| Generated mapping | MAPPED to 3-Hydroxy-3-Methylglutaryl-CoA_Synthase_Deficiency.yaml |
| Candidate DisMech targets | 3-Hydroxy-3-Methylglutaryl-CoA_Synthase_Deficiency.yaml |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents this as HMGCS2-related 3-hydroxy-3-methylglutaryl-CoA synthase deficiency, with alternate labels mitochondrial HMG-CoA synthase deficiency, HMG-CoA synthase deficiency, and mHMGS deficiency. Treatability is marked yes.
The biochemical rows include increased urinary crotonylglycine, increased C2 acylcarnitine, decreased to normal or normal free carnitine, normal long- and medium-chain acylcarnitines, increased ASAT/ALAT, decreased to normal plasma acetoacetate, normal to increased urinary acetoacetate, increased serum free fatty acids, decreased to normal plasma ketones, normal to increased urinary ketones and 3-hydroxybutyric acid, increased urinary 4-hydroxy-6-methyl-2-pyrone, normal to increased adipic and other dicarboxylic acids, and decreased blood/plasma glucose. Clinical rows include coma, coma during ketoacidotic episodes, diarrhea, normal intellectual development, lethargy, liver dysfunction, neonatal seizures, seizures, vomiting, acidosis, and hypoglycemia. Treatment rows list avoiding fasting, dietary precursor restriction, and sick day management.
DisMech phenotype coverage
3-Hydroxy-3-Methylglutaryl-CoA_Synthase_Deficiency.yaml is the correct
target. The local entry models biallelic HMGCS2 loss of mitochondrial
HMG-CoA synthase activity, impaired hepatic ketogenesis during fasting or
illness, hypoketotic metabolic decompensation, hypoglycemia, metabolic
acidosis, vomiting, lethargy, hepatomegaly, seizures, encephalopathy, coma,
dicarboxylic aciduria, 4-hydroxy-6-methyl-2-pyrone, C2/C0 acylcarnitine
pattern, fasting avoidance, sick-day carbohydrate support, acute IV glucose,
dietary fat moderation, carnitine during illness, and genetic counseling.
Concordance and completeness
Judgement: correct mapping with high concordance.
IEMbase and DisMech agree on HMGCS2, impaired ketone-body synthesis, fasting or illness triggered decompensation, low or inadequate ketone production, hypoglycemia, acidosis, vomiting, lethargy, seizures/coma, liver involvement, dicarboxylic aciduria, 4-hydroxy-6-methyl-2-pyrone, C2 acylcarnitine pattern, and fasting/sick-day management. IEMbase adds crotonylglycine, normal long/medium-chain acylcarnitines, normal intellectual development, and dietary precursor restriction as review details.
Curation actions
- Keep the mapping to
3-Hydroxy-3-Methylglutaryl-CoA_Synthase_Deficiency.yaml. - Consider whether crotonylglycine and the normal long/medium-chain acylcarnitine pattern should be added as diagnostic-differential biomarkers.
- Review IEMbase dietary precursor restriction against primary sources before adding it, because the local entry currently emphasizes fasting avoidance and carbohydrate support.