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IEMbase 0599: GMPPB-related muscular dystrophy-dystroglycanopathy

Scope

Field Value
IEMbase ID 599
Nosology 18.4.02.01
Gene GMPPB
External IDs OMIM:615350; OMIM:615351; OMIM:615352; ORPHA:588
Generated mapping CANDIDATE; Dystroglycanopathy.yaml
Candidate DisMech targets Dystroglycanopathy.yaml#MDDG14 (GMPPB); Congenital_Myasthenic_Syndrome.yaml#GMPPB (secondary context)
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents GMPPB-related muscular dystrophy-dystroglycanopathy, also labelled GMPPB-CDG and MDDGA. The record is autosomal recessive, classified under multiple glycosylation pathways, has unknown treatability, and has no treatment rows.

Biochemical rows include increased plasma creatine kinase and muscle hypoglycosylation of alpha-dystroglycan. Clinical rows include hypotonia, muscle weakness, limb-girdle muscular dystrophy, congenital myasthenic syndrome, cataract, epilepsy, cerebellar hypoplasia, microcephaly, intellectual disability, and myoglobinuria.

DisMech phenotype coverage

Dystroglycanopathy.yaml is a valid local target at subtype level. It models the muscular dystrophy-dystroglycanopathy spectrum caused by defective O-mannosylation of alpha-dystroglycan, and explicitly includes MDDG14 (GMPPB), where GMPPB supplies GDP-mannose for the dystroglycan glycosylation pathway. It also includes reduced alpha-dystroglycan glycosylation and broad brain, eye, muscle, seizure, and CK coverage.

Congenital_Myasthenic_Syndrome.yaml provides secondary context because it includes GMPPB among glycosylation-related CMS genes and describes the myasthenic-myopathic limb-girdle presentation. That entry is not the primary disease target for IEMbase 0599, but it is relevant for the congenital myasthenic-syndrome phenotype row.

Concordance and completeness

Judgement: accept the generated candidate as subtype-level local coverage, with secondary CMS context.

The IEMbase record and DisMech agree on gene, recessive inheritance, alpha-dystroglycan hypoglycosylation, muscular dystrophy, and the myasthenic-myopathic overlap. IEMbase adds a concise checklist of GMPPB-specific review prompts that are not all explicit in the local subtype block.

Curation actions

  • Map to Dystroglycanopathy.yaml#MDDG14 (GMPPB) for disease-level import.
  • Use Congenital_Myasthenic_Syndrome.yaml#GMPPB only as secondary phenotype context for the CMS overlap.
  • Preserve creatine kinase, alpha-dystroglycan hypoglycosylation, cataract, cerebellar hypoplasia, microcephaly, epilepsy, intellectual disability, myoglobinuria, limb-girdle weakness, and CMS rows as source-review prompts.