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IEMbase 0237: ETFA-related Electron transfer flavoprotein alpha subunit deficiency

Scope

Field Value
IEMbase ID 237
Nosology 4.2.06.01
Gene ETFA
External IDs OMIM:231680
Generated mapping CANDIDATE; Multiple_Acyl-CoA_Dehydrogenase_Deficiency.yaml
Candidate DisMech targets Multiple_Acyl-CoA_Dehydrogenase_Deficiency.yaml
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents this as ETFA-related electron transfer flavoprotein alpha subunit deficiency, with alternate labels glutaric aciduria type 2A and multiple acyl-CoA dehydrogenase deficiency type 2A. The record is autosomal recessive and treatability is marked yes.

Treatment rows include beta-hydroxybutyrate, carnitine, and riboflavin. Biochemical rows include broad acylglycine elevations, sarcosine in plasma and urine, C4 through C18 acylcarnitine elevations, low or normal free carnitine, creatine kinase and transaminase elevations, low ketones during hypoglycemia, multiple dicarboxylic and organic acids including ethylmalonic, glutaric, adipic, sebacic, suberic, and D-2-hydroxyglutaric acids, and low-normal glucose. Clinical and characteristic rows include congenital brain and kidney anomalies, metabolic acidosis, renal cysts, cardiomyopathy, coma, hypotonia, lethargy, liver dysfunction, exercise-induced rhabdomyolysis, and skeletal myopathy.

DisMech phenotype coverage

Multiple_Acyl-CoA_Dehydrogenase_Deficiency.yaml covers ETFA, ETFB, and ETFDH as causative genes for MADD. It represents the shared electron-transfer defect, blocked transfer of reducing equivalents from multiple flavoprotein dehydrogenases, broad acylcarnitine and organic-acid abnormalities, glutaric and dicarboxylic aciduria, hypoketotic hypoglycemia, metabolic acidosis, hyperammonemia, cardiomyopathy, coma/encephalopathy, hepatic involvement, myopathy/rhabdomyolysis, congenital anomalies, renal cystic dysplasia, and riboflavin-responsive treatment context.

Concordance and completeness

Judgement: accept the generated candidate as the correct file-level target.

IEMbase is subtype-specific for ETFA/MADD type 2A. DisMech currently represents MADD as a shared disease file with gene-specific sections rather than separate ETFA, ETFB, and ETFDH subtype files. That is sufficient for a correct mapping: the gene, mechanism, biomarker pattern, neonatal-congenital spectrum, myopathic features, and treatment context align.

IEMbase adds useful granular prompts for sarcosine, D-2-hydroxyglutaric acid, specific acylglycines, and beta-hydroxybutyrate treatment context.

Curation actions

  • Keep this mapped to Multiple_Acyl-CoA_Dehydrogenase_Deficiency.yaml.
  • If subtype granularity is later added, record this as ETFA-related MADD type 2A/electron transfer flavoprotein alpha subunit deficiency.
  • Consider IEMbase's granular analyte list when refreshing MADD diagnostic markers.