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IEMbase 0497: GYS2-related hepatic glycogen synthase deficiency

Scope

Field Value
IEMbase ID 497
Nosology 3.4.03.01
Gene GYS2
External IDs OMIM:240600; ORPHA:2089
Generated mapping CANDIDATE; MEDIUM; Glycogen_Storage_Disease_Type_I.yaml
Candidate DisMech targets Glycogen_Storage_Disease_Type_I.yaml
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents autosomal recessive GYS2-related hepatic glycogen synthase deficiency as glycogen storage disease type 0a. Treatments are fasting avoidance and a protein-rich diet. Biochemical rows include decreased liver glycogen synthase, increased fasted plasma and urine ketones, decreased-to-normal liver glycogen, decreased fasting glucose, normal-to-increased fed glucose, and increased fed lactate. Clinical rows include absent hepatomegaly, fasting hypoglycemia, and seizures.

DisMech phenotype coverage

Glycogen_Storage_Disease_Type_I.yaml is not the correct target. It models GSD I due to G6PC1/SLC37A4 defects, with hepatic glycogen accumulation, hepatomegaly, lactic acidosis, hyperlipidemia, and hyperuricemia. It does not model GYS2, hepatic glycogen synthase deficiency, GSD 0a, depleted liver glycogen, postprandial lactate/glucose changes, or absent hepatomegaly as a distinguishing feature.

Concordance and completeness

Judgement: false-positive candidate; true GYS2/GSD 0a local gap.

The generated candidate is a carbohydrate-metabolism neighbor but it has an opposite glycogen-storage direction. IEMbase's disease reflects impaired liver glycogen synthesis and reduced hepatic glycogen, whereas GSD I reflects failure to mobilize glucose-6-phosphate and hepatic glycogen/fat accumulation. The absence of hepatomegaly and the fed lactate/glucose pattern make the GSD I candidate particularly misleading.

Curation actions

  • Do not map this record to Glycogen_Storage_Disease_Type_I.yaml.
  • Track GYS2-related hepatic glycogen synthase deficiency / GSD 0a as a local curation gap.
  • Preserve IEMbase prompts for fasting avoidance, protein-rich diet, depleted liver glycogen, fed lactate/glucose, absent hepatomegaly, fasting hypoglycemia, and seizures for a future exact entry.