IEMbase 0057: MCCC1-related 3-methylcrotonyl-CoA carboxylase deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 57 |
| Nosology | 1.2.1.01 |
| Gene | MCCC1 |
| External IDs | OMIM:210200 |
| Generated mapping | CANDIDATE by fuzzy_alias_gene |
| Candidate DisMech targets | 3-Methylcrotonyl-CoA_Carboxylase_Deficiency.yaml |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents this as autosomal recessive MCCC1-related 3-methylcrotonyl-CoA carboxylase 1 deficiency, also called 3-methylcrotonylglycinuria type 1 or MCC A. Treatability is marked yes and the listed prevalence range is 1:50,000-1:30,000 in Europe.
The biochemical signal includes high urinary 3-methylcrotonylglycine, high or normal-high 3-methylcrotonylcarnitine, high C5-OH acylcarnitine in dried blood spot or plasma, normal-high esterified carnitine, low-normal free carnitine, low fibroblast MCCC activity, increased urinary 3-hydroxyisovaleric acid, and possible hyperammonemia, glucose depression, positive anion gap, or base-excess abnormality.
IEMbase does not list a characteristic clinical feature set, but the additional clinical section includes cardiomyopathy, cerebral atrophy, infection-triggered acute encephalopathy, failure to thrive, highly variable expressivity including asymptomatic individuals, hypo- or hypertonia, hypoglycemia, ketoacidosis, metabolic acidosis, metabolic stroke, muscle pain or weakness, neutropenia, acrid urine odor, psychomotor delay, thrombocytopenia, and white-matter MRI changes. Treatments are avoidance of fasting and L-carnitine supplements.
DisMech phenotype coverage
The candidate mapping is correct. DisMech models 3-methylcrotonyl-CoA carboxylase deficiency as a leucine-catabolism disorder caused by MCCC1 or MCCC2 molecular-function deficiency, with accumulation of 3-hydroxyisovaleric acid, 3-methylcrotonylglycine, and C5-OH acylcarnitine.
DisMech covers MCCC1 and MCCC2 genetic causes, newborn-screening biomarker coverage, secondary carnitine deficiency, low penetrance and asymptomatic newborn-screening cases, stress-triggered metabolic decompensation, hypoglycemia, metabolic acidosis, ketoacidosis, hyperammonemia, coma, hypotonia, failure to thrive, developmental regression, movement abnormality, and selected vascular or respiratory complications. Treatments include moderate dietetic modification, carnitine supplementation, and biotin supplementation.
Concordance and completeness
Judgement: generated CANDIDATE should be accepted as the manual mapping to
3-Methylcrotonyl-CoA_Carboxylase_Deficiency.yaml.
The main nuance is granularity: IEMbase is specifically MCCC1/MCC A, while the DisMech file intentionally covers the combined MCCC1/MCCC2 disorder. That is consistent with the project scope unless future subtype anchors are introduced. IEMbase adds some additional candidate phenotype rows, including cardiomyopathy, metabolic stroke, neutropenia, thrombocytopenia, and white-matter MRI changes, but DisMech is broader for mechanism, penetrance, and management.
Curation actions
- Promote this candidate to a correct file-level mapping.
- Keep MCCC1-specific identity as a gene-level note rather than creating a standalone disease file.
- Consider whether the local entry should add an explicit MCCC1/MCC A subtype anchor if downstream crosswalks require gene-specific subtype resolution.