IEMbase 0233: HADHB-related Isolated deficiency of long-chain 3-ketoacyl-CoA thiolase
Scope
| Field | Value |
|---|---|
| IEMbase ID | 233 |
| Nosology | 4.2.06.02 |
| Gene | HADHB |
| External IDs | OMIM:143450 |
| Generated mapping | UNMAPPED; no candidate |
| Candidate DisMech targets | Partial umbrella coverage: Mitochondrial_Trifunctional_Protein_Deficiency.yaml |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents this as HADHB-related isolated deficiency of long-chain 3-ketoacyl-CoA thiolase, with the alternate label LKAT. The record is autosomal recessive and treatability is marked unknown.
The biochemical rows include long-chain hydroxyacylcarnitines, long-chain ketoacylcarnitines, free carnitine, creatine kinase, transaminases, hypoketotic hypoglycemia context, 3-hydroxy dicarboxylic organic acids, glucose, and lactate. Characteristic rows include cardiac arrhythmia, cardiomyopathy, muscular-axial hypotonia, high lethality, liver dysfunction, pulmonary edema, and skeletal myopathy. Treatments listed by IEMbase are a low-LCT diet, MCT formula, sodium-D-L-hydroxybutyrate, and triheptanoin.
DisMech phenotype coverage
Mitochondrial_Trifunctional_Protein_Deficiency.yaml provides partial umbrella
coverage. It covers HADHB as a cause of mitochondrial trifunctional protein
deficiency, the beta subunit of the MTP complex, loss of long-chain
3-ketoacyl-CoA thiolase activity along with the other MTP activities, impaired
long-chain fatty-acid beta-oxidation, elevated long-chain
3-hydroxyacylcarnitines, cardiomyopathy, arrhythmia/cardiac disease context,
hypoglycemia, hepatic dysfunction, neuropathy, myopathy, rhabdomyolysis, MCT
diet, triheptanoin, fasting avoidance, acute glucose support, and genetic
counseling.
The local file does not appear to expose a dedicated isolated long-chain 3-ketoacyl-CoA thiolase/LKAT subtype. That distinction matters because IEMbase frames the record as isolated HADHB thiolase deficiency rather than complete MTP deficiency.
Concordance and completeness
Judgement: partial false negative to local umbrella coverage, with an exact isolated LKAT target missing.
The generated unmapped status misses substantial local HADHB/MTPD mechanism and phenotype coverage. However, mapping this record directly to complete MTPD without a caveat would blur IEMbase's isolated enzyme-defect scope. IEMbase also adds ketoacylcarnitines, pulmonary edema, sodium-D-L-hydroxybutyrate, and low-LCT/MCT formula wording as review prompts.
Curation actions
- Use
Mitochondrial_Trifunctional_Protein_Deficiency.yamlas partial umbrella coverage if a single current DisMech target is required. - Record a gap for an exact isolated HADHB/LKAT subtype or standalone disease concept.
- Do not treat this as fully resolved by complete MTPD unless the crosswalk can preserve the isolated-thiolase scope caveat.