IEMbase 0577: ACSF3-related combined malonic and methylmalonic aciduria
Scope
| Field | Value |
|---|---|
| IEMbase ID | 577 |
| Nosology | 12.1.22.01 |
| Gene | ACSF3 |
| External IDs | OMIM:614245; ORPHA:289504 |
| Generated mapping | UNMAPPED; best candidate 3-Hydroxy-3-Methylglutaryl-CoA_Synthase_Deficiency.yaml |
| Candidate DisMech targets | Combined_Malonic_and_Methylmalonic_Aciduria.yaml |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents ACSF3-related acyl-CoA synthetase 3 deficiency, with alternate label combined malonic and methylmalonic aciduria and abbreviation MMA/MA. The record is autosomal recessive, idiopathic subtype, of unknown treatability, and has no treatment rows.
Biochemical rows include normal blood/plasma propionylcarnitine, increased malonylcarnitine, low-to-normal free carnitine, increased urinary malonic acid, increased plasma and urinary methylmalonic acid, increased urinary MMA/MA ratio, variable base excess, low-to-normal cholesterol and glucose, and normal-to-high plasma lactate. Clinical and characteristic rows include autism spectrum disorder, cardiomyopathy, coma, dystonia, failure to thrive, feeding difficulties, white-matter/brainstem/cerebellar T2 MRI changes, hypoglycemia, axial hypotonia, ketoacidosis, lethargy, liver dysfunction, loss of speech, memory problems, microcephaly, ocular migraine, mild dysmorphic features, seizures, vomiting, developmental delay, and metabolic acidosis.
DisMech phenotype coverage
Combined_Malonic_and_Methylmalonic_Aciduria.yaml is the correct local target.
It models autosomal recessive ACSF3 deficiency, mitochondrial malonyl-CoA /
methylmalonyl-CoA synthetase deficiency, failure to activate malonate and
methylmalonate to CoA thioesters, combined malonic and methylmalonic aciduria,
mitochondrial metabolic inefficiency, and a variable clinical spectrum ranging
from favorable screen-detected outcomes to neurologic or childhood metabolic
presentations.
The generated HMG-CoA synthase candidate is a false positive from organic-acid metabolism similarity and does not match ACSF3/CMAMMA.
Concordance and completeness
Judgement: generated false negative; resolve to
Combined_Malonic_and_Methylmalonic_Aciduria.yaml.
IEMbase and DisMech agree on ACSF3 identity, recessive inheritance, combined malonic and methylmalonic aciduria, elevated malonic and methylmalonic acids, mitochondrial metabolite-repair framing, variable neurologic/metabolic presentation, seizures, developmental delay, failure to thrive, hypoglycemia, ketoacidosis, microcephaly, dystonia, axial hypotonia, and liver dysfunction. DisMech is stronger for the metabolite-activation mechanism and the caution that unselected cohorts may be mild.
IEMbase adds useful prompts for malonylcarnitine, propionylcarnitine normality, free carnitine, cholesterol, lactate, cardiomyopathy, autism, white-matter MRI changes, speech loss, memory problems, ocular migraine, vomiting, and dysmorphic features.
Curation actions
- Promote this record to
Combined_Malonic_and_Methylmalonic_Aciduria.yaml. - Reject
3-Hydroxy-3-Methylglutaryl-CoA_Synthase_Deficiency.yamlas an exact mapping. - Consider reviewing IEMbase acylcarnitine, imaging, cardiomyopathy, neurodevelopmental, and broader clinical prompts against the local generally-mild-course caveat before import.