IEMbase 0041: GLUL-related glutamine synthetase deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 41 |
| Nosology | 1.9.01.01 |
| Gene | GLUL |
| External IDs | OMIM:610015; ORPHA:71278 |
| Generated mapping | UNMAPPED; best fuzzy candidate Lipoic_Acid_Synthetase_Deficiency.yaml |
| Candidate DisMech targets | none currently valid |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents GLUL deficiency as glutamine synthetase deficiency. The biochemical signature is markedly low plasma glutamine, low CSF glutamine, low urinary glutamine, normal CSF and plasma glutamic acid, and normal-to-high blood ammonia.
The phenotype is severe and early: absent head control, developmental delay, epileptic encephalopathy, intractable epilepsy, neonatal seizures, abnormal EEG, possible cerebellar hypoplasia, and possible necrotising erythema. IEMbase lists glutamine as a nutritional treatment. Prevalence is listed as 1:2,000,000.
DisMech phenotype coverage
There is no current DisMech entry or subtype for GLUL-related glutamine
synthetase deficiency. The generated fuzzy candidate,
Lipoic_Acid_Synthetase_Deficiency.yaml, should be rejected. LIAS deficiency is
a mitochondrial lipoylation disorder with lipoate-dependent enzyme defects,
lactic acidosis, hyperglycinemia, neonatal epilepsy, and combined dehydrogenase
impairment. GLUL deficiency is a glutamine synthesis disorder with systemic and
CSF glutamine depletion.
Several local urea-cycle entries mention astrocytic glutamine synthetase as part of ammonia detoxification, and citrin deficiency discusses impaired glutamine synthetase function as a downstream state, but none of those entries represent primary GLUL deficiency.
Concordance and completeness
Judgement: generated unmapped status is correct, and the LIAS candidate is a false positive.
IEMbase provides a strong future curation target. The most important phenotype contrast is low glutamine with epileptic encephalopathy, not the high glycine and lactic-acidosis profile of mitochondrial lipoylation defects.
Curation actions
- Do not map this record to
Lipoic_Acid_Synthetase_Deficiency.yaml. - Consider GLUL deficiency as a future high-value metabolic encephalopathy target because it has severe clinical expression and a clear biochemical signature.
- If curated, capture glutamine supplementation separately from generic supportive epilepsy management.