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IEMbase 0512: GSS-related Glutathione synthetase deficiency, severe

Scope

Field Value
IEMbase ID 512
Nosology 2.1.02.02
Gene GSS
External IDs OMIM:266130; ORPHA:32
Generated mapping UNMAPPED; best candidate Hereditary_Orotic_Aciduria.yaml
Candidate DisMech targets No exact local target found
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents this as severe GSS-related glutathione synthetase deficiency, with alternate labels 5-oxoprolinuria and pyroglutamic aciduria. Treatability is marked yes, though no treatment rows are listed in the cached JSON.

The biochemical rows include very markedly decreased glutathione synthetase activity in fibroblasts and RBCs, very low RBC glutathione, very markedly increased urinary 5-oxoproline, low hemoglobin, high reticulocytes, and high lactate. The clinical and clinical-characteristic rows add acidosis, lactic acidosis, hemolytic anemia, recurrent bacterial infections, neurological symptoms, psychomotor delay, seizures, ataxia, tone abnormalities, myopathy, corneal clouding, pigmentary retinopathy, night blindness, and jaundice.

DisMech phenotype coverage

No dedicated GSS or glutathione synthetase deficiency entry was found in kb/disorders. The generated candidate Hereditary_Orotic_Aciduria.yaml is not valid because it covers UMPS-related pyrimidine synthesis failure and orotic acid overexcretion, not glutathione synthesis failure or 5-oxoprolinuria.

5-Oxoprolinase_Deficiency.yaml is a useful gamma-glutamyl-cycle neighbor and differential diagnosis because both OPLAH and GSS defects can produce 5-oxoprolinuria. It is not an exact target for this GSS disease.

Concordance and completeness

Judgement: true local gap.

The earlier mild GSS IEMbase record also resolved as a local gap. This severe record strengthens the same gap and adds multisystem severity: metabolic/lactic acidosis, neurological disease, recurrent infections, and ocular findings on top of the core GSS enzyme deficiency, low glutathione, urinary 5-oxoproline, and hemolytic anemia signal.

Curation actions

  • Add GSS-related glutathione synthetase deficiency as a future local disease, with mild and severe phenotype branches if the spectrum is curated.
  • Reject Hereditary_Orotic_Aciduria.yaml as a metabolite-neighbor false candidate.
  • Use 5-Oxoprolinase_Deficiency.yaml only as pathway/differential context.
  • Preserve severe-form prompts for acidosis, lactic acidosis, recurrent infections, seizures, psychomotor delay, tone abnormalities, myopathy, and ocular involvement.