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IEMbase 0216: GCLC-related Gamma-glutamylcysteine synthetase deficiency

Scope

Field Value
IEMbase ID 216
Nosology 2.1.01.01
Gene GCLC
External IDs OMIM:230450
Generated mapping UNMAPPED; best candidate Carbamoyl_Phosphate_Synthetase_I_Deficiency.yaml
Candidate DisMech targets No valid local target found
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents this as GCLC-related gamma-glutamylcysteine synthetase deficiency, with alternate labels glutamate-cysteine ligase deficiency, hemolytic anemia due to GGCS deficiency, and GGCS. The record is autosomal recessive and treatability is marked unknown.

The biochemical rows include markedly decreased gamma-glutamyl-cysteine synthetase activity in fibroblasts and RBCs, markedly decreased RBC glutathione, low hemoglobin, increased reticulocytes, and normal-to-increased plasma amino acids. Characteristic clinical rows include hemolytic anemia and jaundice, with additional rows for ataxia, psychotic behavior, myopathy, and neurocognitive/behavioral issues. No treatment rows are listed in the cached record.

DisMech phenotype coverage

No dedicated GCLC or gamma-glutamylcysteine synthetase deficiency disorder was found in kb/disorders. The generated candidate Carbamoyl_Phosphate_Synthetase_I_Deficiency.yaml is not valid: it covers CPS1 proximal urea-cycle disease with hyperammonemia, low citrulline, and normal or low orotic acid, not GCLC/glutathione-biosynthesis disease. Nearby local gamma-glutamyl-cycle content in 5-Oxoprolinase_Deficiency.yaml is OPLAH-specific and does not cover GCLC deficiency.

Concordance and completeness

Judgement: true local gap.

IEMbase provides a coherent GCLC deficiency profile anchored on enzyme deficiency, low RBC glutathione, hemolytic anemia, reticulocytosis, jaundice, and optional neurologic/psychiatric features. The local CPS1 candidate shares only a synthetase-word lexical overlap and is mechanistically unrelated.

Curation actions

  • Add GCLC-related gamma-glutamylcysteine synthetase deficiency as a future local disease if glutathione-cycle disorders are curated.
  • Reject Carbamoyl_Phosphate_Synthetase_I_Deficiency.yaml as a false candidate.
  • Use IEMbase as a lead for RBC glutathione, enzyme-activity, hemolytic anemia, reticulocyte, and jaundice rows.