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IEMbase 0362: PRPS1 superactivity

Scope

Field Value
IEMbase ID 362
Nosology 16.2.01.01
Gene PRPS1
External IDs OMIM:300661; ORPHA:99014
Generated mapping CANDIDATE/MEDIUM to PRPS1_Superactivity.yaml
Candidate DisMech targets PRPS1_Superactivity.yaml
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents PRPS1-related phosphoribosyl pyrophosphate synthetase 1 superactivity, an X-linked recessive purine-metabolism disorder. Characteristic rows include sensorineural deafness, facial dysmorphism, gout, urine hypoxanthine, plasma uric acid, and urine uric acid.

Additional clinical rows include ataxia, developmental delay, intellectual disability, and urolithiasis. Biochemical rows include urine hypoxanthine, PRPP synthase activity in fibroblasts, PRPP synthase activity in red blood cells, phosphoribose pyrophosphate in red blood cells, plasma uric acid, and urine uric acid. The IEMbase source row spells phosphoribose as "Phosporibose". No treatment rows are present.

DisMech phenotype coverage

The generated candidate is the correct target despite being marked medium confidence. DisMech has a PRPS1 Superactivity file describing X-linked PRPS1 gain-of-function or transcriptional overactivity, increased PRPP, increased de novo purine nucleotide synthesis, and uric acid overproduction.

Local coverage includes mild and severe disease, hyperuricemia, hyperuricosuria, uric acid crystalluria/nephrolithiasis, gout, developmental delay, intellectual disability, sensorineural hearing loss, hypotonia, and ataxia. Local mechanism is stronger for allosteric PRS-I dysregulation and purine overproduction.

Concordance and completeness

Judgement: accept the candidate as the correct DisMech mapping.

The resources agree on PRPS1 identity, X-linked inheritance, PRPP synthetase superactivity, uric acid overproduction, gout, urolithiasis/nephrolithiasis, sensorineural deafness, ataxia, developmental delay, and intellectual disability. IEMbase is more granular for assay material and specimen-specific hypoxanthine/uric-acid rows.

Curation actions

  • Map this record to PRPS1_Superactivity.yaml.
  • Consider future enrichment with urine hypoxanthine, PRPP synthase activity in fibroblasts and red blood cells, red-cell PRPP, and specimen-specific plasma versus urine uric-acid rows after source verification.
  • Treat absent IEMbase treatment rows as incomplete IEMbase coverage rather than a contradiction of any local urate-lowering management context.