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IEMbase 0664: BCKDK-related branched-chain ketoacid dehydrogenase kinase deficiency

Scope

Field Value
IEMbase ID 664
Nosology 1.3.06.01
Nosology code IEM0112
Gene BCKDK
External IDs OMIM:614923; ORPHA:308410
Generated mapping MAPPED to BCKDK_Deficiency.yaml
Candidate DisMech targets BCKDK_Deficiency.yaml
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents autosomal recessive BCKDK-related branched-chain ketoacid dehydrogenase kinase deficiency.

The biochemical signature is decreased plasma isoleucine, leucine, and valine across infancy, childhood, and adolescence. Clinical rows emphasize autism, intellectual disability, delayed or abnormal speech, and possible seizures and stereotyped hand movements.

DisMech phenotype coverage

BCKDK_Deficiency.yaml is an exact local target. It models loss of the kinase that normally phosphorylates and inhibits BCKDH, causing constitutive BCKDH activation, excessive branched-chain amino-acid catabolism, and low plasma/CSF leucine, isoleucine, and valine.

The local phenotype set includes autistic behavior, intellectual disability, global developmental delay, epileptic encephalopathy, seizures, microcephaly, and the biochemical low-BCAA pattern. It also records BCAA-enriched nutritional support and related treatment cautions.

Concordance and completeness

Judgement: exact high-concordance mapping.

IEMbase and DisMech agree on the inverse MSUD-like biochemical direction: BCKDK loss lowers BCAAs rather than increasing them. DisMech is richer for mechanism and treatment. IEMbase adds row-level reminders for delayed or absent speech and stereotyped hand movements that should be checked before claiming phenotype completeness.

Curation actions

  • Keep BCKDK_Deficiency.yaml as the disease-level target.
  • Preserve low leucine, isoleucine, and valine as the defining biochemical signature.
  • Review whether speech abnormality and stereotyped hand movements are captured explicitly enough in the local phenotype model.
  • Keep this separate from MSUD and PPM1K mild MSUD despite shared BCKDH pathway biology.