Skip to content

IEMbase 0032: GLDC-related nonketotic hyperglycinemia

Scope

Field Value
IEMbase ID 32
Nosology 1.6.01.01
Gene GLDC
External IDs OMIM:238300
Generated mapping MAPPED by alias_exact:glycine encephalopathy
Candidate DisMech targets Nonketotic_Hyperglycinemia.yaml
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents GLDC-related glycine cleavage system deficiency. The characteristic phenotype set includes seizures, hypotonia, burst-suppression EEG, hypsarrhythmia, multifocal epilepsy, corpus callosum agenesis or hypoplasia, and severe neonatal/infantile neurologic involvement.

Additional features include apnea, feeding difficulties, hiccups, lethargy, psychomotor delay, neurologic deterioration, drug-resistant epilepsy, hydrocephalus, posterior fossa anomalies, simplified gyral pattern, ataxia, chorea, spasticity, hyperactivity, optic atrophy, and elevated CSF glycine, plasma glycine, and CSF/plasma glycine ratio. Treatments listed are sodium benzoate and dextromethorphan/NMDA-antagonist therapy.

DisMech phenotype coverage

The generated mapping to Nonketotic_Hyperglycinemia.yaml is correct. DisMech covers glycine cleavage system dysfunction, systemic and CNS glycine accumulation, plasma and CSF glycine, CSF-to-plasma glycine ratio, seizures, hypotonia, lethargy, apnea, global developmental delay, intellectual disability, abnormal corpus callosum morphology, cerebral white-matter abnormality, burst-suppression EEG, ADHD-like behavior, neonatal respiratory distress, recurrent singultus, sodium benzoate, ketogenic diet, NMDA antagonist therapy with caveats, anticonvulsant management, supportive care, and genetic counseling.

Concordance and completeness

Judgement: correct mapping and high concordance. DisMech is strong mechanistically and therapeutically; IEMbase is richer for specific imaging and EEG subfeatures.

IEMbase adds hypsarrhythmia, multifocal epilepsy, drug-resistant epilepsy, feeding difficulties, hydrocephalus, posterior fossa anomalies, simplified gyral pattern, optic atrophy, chorea, spasticity, and explicit corpus-callosum agenesis/hypoplasia labels. DisMech adds D-serine and one-carbon metabolism context, glial-lineage developmental mechanisms, GCSH/lipoylation detail, ketogenic diet, anticonvulsant cautions, and broader supportive care.

Curation actions

  • Keep the generated mapping.
  • Consider adding selected EEG and MRI features from IEMbase, especially hypsarrhythmia, multifocal epilepsy, posterior fossa anomalies, hydrocephalus, and simplified gyral pattern.
  • Consider adding feeding difficulty, drug-resistant epilepsy, optic atrophy, chorea, and spasticity if supported by NKH evidence.