| Category | Feature | Suggested ontology term(s) | Notes | Supporting source |
|---|---|---|---|---|
| Phenotype | Autism spectrum disorder / autistic features | HPO: Autism (HP:0000717); Autistic behavior (HP:0000729) | Human cases were initially ascertained with autism/ASD together with ID and epilepsy; later reports also describe ASD in affected siblings. | (pqac-00000005, pqac-00000006, pqac-00000002) |
| Phenotype | Developmental delay / intellectual disability | HPO: Global developmental delay (HP:0001263); Intellectual disability (HP:0001249) | Core neurodevelopmental phenotype across reported families; severe developmental delay and adaptive impairment recur in case series. | (pqac-00000005, pqac-00000006, pqac-00000003) |
| Phenotype | Epilepsy / seizures | HPO: Seizure (HP:0001250); Epileptic encephalopathy (HP:0200134) | Early generalized seizures and epileptic encephalopathy were reported; seizure burden improved with treatment in some patients. | (pqac-00000003, pqac-00000004, pqac-00000005) |
| Phenotype | Microcephaly | HPO: Microcephaly (HP:0000252); Progressive microcephaly (HP:0000253) | Postnatal/progressive microcephaly is a recurrent feature in human cases and mouse models. | (pqac-00000003, pqac-00000002, pqac-00000008) |
| Phenotype | Absent speech / severe language impairment | HPO: Absent speech (HP:0001344); Severe expressive language delay (HP:0011344) | The 2022 sibling series described absent speech; severe speech/language delay is repeatedly noted in case descriptions. | (pqac-00000003, pqac-00000001) |
| Phenotype | Motor abnormalities / hindlimb clasping | HPO: Abnormality of movement (HP:0100022); Motor delay (HP:0001270) | Mouse and rat models show hindlimb clasping/flexion-extension or splaying; in humans, psychomotor delay is prominent. | (pqac-00000012, pqac-00000013, pqac-00000014) |
| Laboratory abnormality | Low plasma/CSF branched-chain amino acids | HPO: Decreased circulating branched chain amino acid concentration (suggested); Decreased CSF branched chain amino acid concentration (suggested) | Explicit biochemical hallmark: low leucine, isoleucine, and valine in plasma and CSF; newborn DBS can also show low Xle/valine. | (pqac-00000017, pqac-00000018, pqac-00000022) |
| Mechanism | Increased BCKDH activity due to loss of inhibitory phosphorylation | GO BP: branched-chain amino acid catabolic process (GO:0009083); protein phosphorylation (GO:0006468) | BCKDK loss reduces inhibitory phosphorylation of BCKDH E1α, increasing catabolic flux through BCKDH. | (pqac-00000012, pqac-00000013, pqac-00000009) |
| Mechanism | Mitochondrial involvement | GO CC: mitochondrion (GO:0005739); mitochondrial matrix (GO:0005759) | BCKDK is mitochondrial; patient fibroblasts and models show mitochondrial defects, and BCKDH regulation occurs in the mitochondrial compartment. | (pqac-00000009, pqac-00000011) |
| Mechanism | Blood-brain barrier transport limitation for BCAA repletion | GO BP: amino acid transmembrane transport (GO:0003333) | 2024 mouse work suggests enteral BCAA supplementation may not adequately restore CSF/brain BCAA, implicating BBB transport limits; BBB transporters are discussed in the original Science report. | (pqac-00000008, pqac-00000012) |
| Cell type | Neuron involvement | CL: neuron (CL:0000540); cortical neuron (suggested CL class) | Neuronal deficiency is strongly implicated; cortex-neuron restricted Bckdk loss causes neurological abnormalities in mice. | (pqac-00000011) |
| Anatomy | Cerebral cortex / brain | UBERON: brain (UBERON:0000955); cerebral cortex (UBERON:0000956); cerebrospinal fluid (UBERON:0001359) | Neurologic phenotype localizes chiefly to brain/CNS; low CSF BCAA and cortex-neuron experiments support these anatomy terms. | (pqac-00000017, pqac-00000011, pqac-00000013) |
| Anatomy | Peripheral nervous system | UBERON: peripheral nervous system (UBERON:0000010) | Rat model demonstrates both central and peripheral nervous system involvement. | (pqac-00000013) |


*Table: This table maps the main reported clinical and mechanistic features of BCKDK deficiency to suggested ontology terms for phenotype, process, cell type, and anatomy. It is useful for structuring disease-knowledge-base annotations while staying close to the available evidence.*