IEMbase 0165: L2HGDH-related L-2-hydroxyglutaric aciduria
Scope
| Field | Value |
|---|---|
| IEMbase ID | 165 |
| Nosology | 12.1.02.01 |
| Gene | L2HGDH |
| External IDs | OMIM:236792; ORPHA:79314 |
| Generated mapping | MAPPED to L-2-Hydroxyglutaric_Aciduria.yaml |
| Candidate DisMech targets | L-2-Hydroxyglutaric_Aciduria.yaml |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents this as L2HGDH-related L-2-hydroxyglutarate dehydrogenase deficiency, with alternate labels L-2-hydroxyglutaric aciduria and L2HGA. Treatability is marked yes, but the local IEMbase JSON does not list treatment rows for this disorder.
The biochemical rows show increased L-2-hydroxyglutaric acid in CSF, plasma, and urine; CSF and plasma lysine reported as normal to normal-increased; neonatal ammonia and lactate reported as normal to increased; and increased CSF protein in infancy and childhood. Clinical rows include dentate nucleus lesions, globus pallidus lesions, cerebellar white-matter MRI abnormalities, intellectual disability, ataxia, dysarthria, tremor, dystonia, choreoathetosis, seizures, hypotonia, spasticity, macrocephaly, and gliomas.
DisMech phenotype coverage
L-2-Hydroxyglutaric_Aciduria.yaml is the correct target. It models biallelic
L2HGDH pathogenic variants, loss of mitochondrial L-2-hydroxyglutarate
dehydrogenase metabolite-repair activity, L-2-HG accumulation in urine, plasma,
CSF, and brain, selective white-matter vulnerability with basal ganglia and
dentate nucleus involvement, intellectual disability, psychomotor delay,
seizures/epilepsy, cerebellar ataxia, dystonia, dysarthria, tremor, chorea,
macrocephaly, spasticity, increased CNS neoplasm risk, riboflavin,
levocarnitine, supportive care, and movement-disorder interventions such as
deep brain stimulation.
Concordance and completeness
Judgement: correct mapping with high concordance.
The IEMbase and DisMech profiles agree on L2HGDH, L-2-HG accumulation in urine, plasma, and CSF, white-matter disease, dentate/basal ganglia involvement, intellectual disability, seizures, ataxia, dystonia/movement disorder, dysarthria, tremor, macrocephaly, spasticity, and glioma/CNS tumor risk. DisMech is stronger for metabolite-repair mechanism, treatment rationale, and neoplasm-risk discussion. IEMbase adds lysine, neonatal ammonia/lactate, CSF protein, and choreoathetosis as potential review details.
Curation actions
- Keep the mapping to
L-2-Hydroxyglutaric_Aciduria.yaml. - Consider future biomarker refinement for lysine, neonatal ammonia/lactate, and CSF protein if primary sources support them.
- Review whether IEMbase choreoathetosis should be represented as a distinct movement-disorder phenotype or covered by the existing chorea/dystonia rows.