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IEMbase 0604: DPM2-related dolichol-P-mannose synthase-2 deficiency

Scope

Field Value
IEMbase ID 604
Nosology 18.4.06.02
Gene DPM2
External IDs OMIM:615042; ORPHA:329178
Generated mapping UNMAPPED; best candidate Dystroglycanopathy.yaml#DPM2-related dystroglycanopathy
Candidate DisMech targets Dystroglycanopathy.yaml#DPM2-related dystroglycanopathy
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents DPM2-related dolichol-P-mannose synthase-2 deficiency, labelled DPM2-CDG. The record is autosomal recessive, classified under disorders of multiple glycosylation pathways, has unknown treatability, and has no treatment rows.

Biochemical rows include increased creatine kinase, increased transaminases, serum sialotransferrin type 1 pattern, and increased dolichol-linked Man5GlcNAc2. Clinical rows include muscular dystrophy, hypotonia, epilepsy, cerebral atrophy on MRI, microcephaly, hepatomegaly, dysmorphic features, joint contractures, scoliosis, strabismus, respiratory distress, and recurrent respiratory infections.

DisMech phenotype coverage

The generated status is a false negative because Dystroglycanopathy.yaml explicitly includes DPM2-related dystroglycanopathy. The subtype states that DPM2 encodes a regulatory subunit of dolichol-phosphate mannose synthase and that variants cause CDG with secondary dystroglycanopathy, severe muscular dystrophy, seizures, intellectual disability, and broader CDG manifestations.

That local coverage is close to the IEMbase disease identity, but it is embedded inside the dystroglycanopathy umbrella. The IEMbase record adds DPM2-CDG-specific biochemical prompts, especially the type 1 sialotransferrin pattern and dolichol-linked Man5GlcNAc2 accumulation, plus hepatomegaly, infection, and respiratory rows that may need source-level review before import.

Concordance and completeness

Judgement: resolve as subtype-level local coverage; generated mapping missed an existing DPM2 target.

The local DPM2 subtype and IEMbase record agree on gene, recessive inheritance, dolichol-phosphate-mannose pathway, CDG/dystroglycanopathy overlap, severe muscle disease, seizures, neurodevelopmental involvement, and broader systemic features. Completeness is limited by the local subtype being less granular than the IEMbase biochemical and clinical rows.

Curation actions

  • Map to Dystroglycanopathy.yaml#DPM2-related dystroglycanopathy as the current local target.
  • Treat DPM2-CDG as subtype-level coverage, not a new unrelated disease.
  • Preserve type 1 sialotransferrin, dolichol-linked Man5GlcNAc2, creatine kinase, transaminases, hepatomegaly, respiratory distress/infections, joint contractures, scoliosis, strabismus, microcephaly, cerebral atrophy, epilepsy, hypotonia, and muscular-dystrophy prompts.