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IEMbase 0097: GRHPR-related glyoxylate reductase/hydroxypyruvate reductase deficiency

Scope

Field Value
IEMbase ID 97
Nosology 13.1.01.01
Gene GRHPR
External IDs OMIM:260000
Generated mapping UNMAPPED; best fuzzy candidate Pyruvate_Dehydrogenase_Deficiency.yaml
Candidate DisMech targets Primary_Hyperoxaluria_Type_2.yaml; Disorders_of_Glyoxylate_and_Oxalate_Metabolism.yaml
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents this as autosomal recessive GRHPR-related glyoxylate reductase/hydroxypyruvate reductase deficiency, with alternate labels primary hyperoxaluria type 2, D-glycerate dehydrogenase deficiency, and PH2. Treatability is marked unknown and no treatment rows are listed.

The characteristic biochemical rows are plasma and urinary oxalic acid and urinary glyceric acid. The wider panel also includes plasma glyceric acid, creatinine, and urea.

The characteristic clinical rows include failure to thrive, growth retardation, nephrocalcinosis, nephrolithiasis, radiolucent metaphyseal bands, and renal colic.

DisMech phenotype coverage

The generated UNMAPPED status is a false negative. The best local disease target is Primary_Hyperoxaluria_Type_2.yaml, with Disorders_of_Glyoxylate_and_Oxalate_Metabolism.yaml as grouping context.

DisMech models PH2 as biallelic GRHPR deficiency disrupting glyoxylate-to- glycolate and hydroxypyruvate-to-D-glycerate flux, producing increased urinary oxalate and L-glycerate. The disease entry covers hyperoxaluria, calcium oxalate nephrolithiasis, nephrocalcinosis, kidney failure, and systemic oxalate deposition. The grouping explicitly differentiates GRHPR/PH2 from the AGXT/PH1 mechanism.

Pyruvate_Dehydrogenase_Deficiency.yaml is a lexical false-positive candidate from "hydroxypyruvate" and should not be used.

Concordance and completeness

Judgement: false-negative mapping with high local mechanistic coverage.

DisMech is strong for the core gene, pathway, oxalate/glycerate chemistry, and kidney-stone mechanism. IEMbase adds plasma-versus-urine compartment detail and additional clinical rows such as growth retardation, renal colic, and radiolucent metaphyseal bands.

Curation actions

  • Update the mapping logic or manual crosswalk to resolve this record to Primary_Hyperoxaluria_Type_2.yaml.
  • Keep Disorders_of_Glyoxylate_and_Oxalate_Metabolism.yaml as grouping context.
  • Consider adding explicit glyceric-acid biomarkers and the IEMbase renal-colic and skeletal-imaging clinical rows if evidence supports them.