IEMbase 0438: ACAD9-related Acyl-CoA dehydrogenase 9 deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 438 |
| Nosology | 7.1.09.01 |
| Gene | ACAD9 |
| External IDs | OMIM:611126; ORPHA:99901 |
| Generated mapping | UNMAPPED; low candidate Glutaryl-CoA_Dehydrogenase_Deficiency.yaml |
| Candidate DisMech targets | ACAD9_Deficiency.yaml |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents autosomal recessive ACAD9 deficiency as a complex I assembly disorder with hypoglycemia and lactic acidosis. Biochemical rows include increased plasma and urine lactate, increased lactate/pyruvate ratio, increased alanine, decreased free carnitine, increased long-chain acylcarnitines, increased creatine kinase, transaminase elevation, ketosis-related organic acids, hyperammonemia, and hypoglycemia. Clinical rows include dilated cardiomyopathy, encephalopathy, exercise intolerance, failure to thrive, hearing loss, axial hypotonia, liver dysfunction or failure including Reye-like liver failure, neurologic dysfunction, rhabdomyolysis, and skeletal myopathy. IEMbase records riboflavin as a treatment row.
DisMech phenotype coverage
ACAD9_Deficiency.yaml is the correct local target. It describes biallelic
ACAD9 disease as a mitochondrial complex I assembly-factor disorder, not as a
primary fatty-acid beta-oxidation defect, and covers complex I deficiency,
oxidative phosphorylation failure, cardiomyopathy, exercise intolerance, lactic
acidosis, muscular weakness, and riboflavin responsiveness.
The generated Glutaryl-CoA_Dehydrogenase_Deficiency.yaml candidate is a false
positive. Local GCDH deficiency is glutaric acidemia type 1, with lysine,
hydroxylysine, and tryptophan catabolism, glutaric acid and
3-hydroxyglutaric acid biomarkers, and encephalopathic crises. It does not
represent ACAD9 complex I assembly disease.
Concordance and completeness
Judgement: false negative; resolve IEMbase 438 to ACAD9_Deficiency.yaml.
The local target has high mechanism and treatment concordance for the core complex I/riboflavin-responsive disorder. IEMbase adds useful phenotypic prompts for long-chain acylcarnitines, hypoglycemia, liver dysfunction, Reye-like liver failure, rhabdomyolysis, and hearing loss that should be checked against primary evidence before import.
Curation actions
- Map IEMbase 438 to
ACAD9_Deficiency.yaml. - Do not map to
Glutaryl-CoA_Dehydrogenase_Deficiency.yaml. - If importing IEMbase-derived prompts, prioritize ACAD9 complex I assembly, lactic acidosis, cardiomyopathy, skeletal myopathy, exercise intolerance, riboflavin responsiveness, and verify the liver, hearing, rhabdomyolysis, hypoglycemia, and acylcarnitine rows against source evidence.