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IEMbase 0232: HADHA-related Trifunctional protein subunit alpha deficiency

Scope

Field Value
IEMbase ID 232
Nosology 4.2.05.02
Gene HADHA
External IDs OMIM:609015
Generated mapping UNMAPPED; best candidate Mitochondrial_Trifunctional_Protein_Deficiency.yaml
Candidate DisMech targets Mitochondrial_Trifunctional_Protein_Deficiency.yaml; Long-Chain_3-Hydroxyacyl-CoA_Dehydrogenase_Deficiency.yaml
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents this as HADHA-related trifunctional protein subunit alpha deficiency. The source label contains an alpha-wording artifact, and the alternate label explicitly spans long-chain hydroxyacyl-CoA dehydrogenase deficiency or complete mitochondrial trifunctional protein deficiency. The record is autosomal recessive and treatability is marked yes, but no treatment rows are attached in the cached JSON.

The biochemical rows include multiple long-chain hydroxyacylcarnitines, palmitoylcarnitine, C14:1, free carnitine, creatine kinase, transaminases, hypoketotic hypoglycemia context, 3-hydroxy dicarboxylic organic acids, ammonia, glucose, and lactate. Clinical rows include intrauterine cardiomyopathy, intrauterine growth restriction, lactic acidosis, and maternal HELLP syndrome. Characteristic rows include cardiac arrhythmia, cardiomyopathy, coma, lethargy, liver dysfunction, peripheral neuropathy, pigmentary retinopathy, and skeletal myopathy.

DisMech phenotype coverage

Local coverage is split across two relevant entries. Mitochondrial_Trifunctional_Protein_Deficiency.yaml covers complete MTP/TFP deficiency caused by HADHA or HADHB variants, loss of the long-chain enoyl-CoA hydratase, LCHAD, and long-chain 3-ketoacyl-CoA thiolase activities, elevated long-chain 3-hydroxyacylcarnitines, cardiomyopathy, hypoglycemia, hepatic dysfunction, neuropathy, rhabdomyolysis, retinopathy, maternal HELLP/acute fatty liver of pregnancy context, MCT-based diet, triheptanoin, fasting avoidance, glucose support, and genetic counseling.

Long-Chain_3-Hydroxyacyl-CoA_Dehydrogenase_Deficiency.yaml covers isolated HADHA/LCHAD deficiency, especially the common c.1528G>C variant, with long-chain 3-hydroxyacylcarnitines, hypoketotic hypoglycemia, cardiomyopathy, hepatopathy, rhabdomyolysis, peripheral neuropathy, progressive chorioretinopathy, dietary fat restriction with MCT supplementation, triheptanoin, fasting avoidance, and pregnancy-related maternal complications.

Concordance and completeness

Judgement: generated unmapped status is a false negative, but the IEMbase label scope is broader than a single clean local target.

If the intended IEMbase concept is complete HADHA-related MTP deficiency, Mitochondrial_Trifunctional_Protein_Deficiency.yaml is the best mapping. If the intended concept is isolated HADHA/LCHAD deficiency, the better mapping is Long-Chain_3-Hydroxyacyl-CoA_Dehydrogenase_Deficiency.yaml. The IEMbase alternate label explicitly combines both, so a single mapping should carry a scope caveat or a secondary target.

Curation actions

  • Treat this as a false negative to existing local fatty-acid-oxidation coverage, not a true disease gap.
  • Prefer Mitochondrial_Trifunctional_Protein_Deficiency.yaml for the complete MTP wording, with Long-Chain_3-Hydroxyacyl-CoA_Dehydrogenase_Deficiency.yaml as secondary context for isolated HADHA/LCHAD disease.
  • Consider splitting or annotating the IEMbase crosswalk if the curation model needs distinct isolated LCHAD versus complete MTP targets.