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IEMbase 0033: PHGDH-related 3-phosphoglycerate dehydrogenase deficiency

Scope

Field Value
IEMbase ID 33
Nosology 1.6.01.02
Gene PHGDH
External IDs OMIM:601815
Generated mapping UNMAPPED
Candidate DisMech targets none currently valid
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents PHGDH deficiency as a serine-biosynthesis disorder. The biochemical signature is the strongest anchor: very low CSF serine, low CSF glycine, low CSF 5-methyltetrahydrofolate, decreased N-acetylaspartate/creatine ratio on MRS, and increased choline/creatine ratio on MRS.

The clinical and imaging pattern is severe and neurodevelopmental. IEMbase marks absent or delayed myelination, cortical and subcortical atrophy, microcephaly, neonatal/infantile seizures, multifocal epilepsy, hypsarrhythmia, Lennox-Gastaut syndrome, megaloblastic anemia, psychomotor delay, spastic tetraplegia, nystagmus, cataract, adducted thumbs, hyperexcitability, ataxia, hypogonadism, and chronic axonal sensorimotor polyneuropathy. Treatments listed are nutritional glycine and L-serine.

DisMech phenotype coverage

There is no current DisMech entry or subtype for PHGDH-related 3-phosphoglycerate dehydrogenase deficiency. Local references to PHGDH occur in other biological contexts, such as serine-biosynthesis reprogramming in Ewing sarcoma, but those are not disease-entity matches. Nonketotic hyperglycinemia also discusses serine-glycine-one-carbon metabolism, but its primary mechanism is glycine cleavage system dysfunction, not PHGDH deficiency.

Concordance and completeness

Judgement: generated unmapped status is correct. This is a missing DisMech curation target, not a low-confidence match to an existing entry.

IEMbase already provides a useful future curation scaffold: the disease is defined by low CSF serine with severe early neurologic disease, myelination failure, epilepsy/EEG abnormalities, microcephaly, and serine/glycine supplementation. DisMech has no valid local phenotype completeness baseline for this entity.

Curation actions

  • Do not map this record to NKH or to cancer metabolic-reprogramming entries that mention PHGDH.
  • Consider a future serine-biosynthesis disorder entry or grouping covering PHGDH, PSAT1, and PSPH deficiencies.
  • If curated, preserve the CSF serine/5-MTHF and MRS markers because they carry more entity-specific signal than the broad seizure/developmental-delay phenotype.