Skip to content

IEMbase 0648: VPS33A-related mucopolysaccharidosis-plus syndrome

Scope

Field Value
IEMbase ID 648
Nosology 19.4.12.02
Gene VPS33A
External IDs OMIM:617303; ORPHA:505248
Generated mapping UNMAPPED; weak candidate Hurler_syndrome.yaml
Candidate DisMech targets False exact candidate; possible MPS grouping context
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents VPS33A-related mucopolysaccharidosis-plus syndrome as an autosomal recessive complex-molecule degradation disorder.

Biochemical rows show markedly increased heparan sulfate in plasma and urine, increased total urinary GAGs, increased urinary dermatan sulfate, and increased urinary oligosaccharides including N-acetylneuraminic acid. Clinical rows combine an MPS-like storage phenotype with severe extra features: coarse facial features, hepatosplenomegaly, dysostosis multiplex, macroglossia, hirsutism, short stature, joint contractures, anemia, thrombocytopenia, bone marrow hypoplasia, foam cells, lymphocyte granulation, proteinuria, hypertrophic cardiomyopathy, congenital heart defects, heart failure, recurrent respiratory infections, respiratory dysfunction, developmental delay, pyramidal signs, and optic atrophy.

DisMech phenotype coverage

Hurler_syndrome.yaml is not an exact target. It correctly overlaps on MPS-like features such as heparan/dermatan sulfate storage, coarse facies, dysostosis multiplex, hepatosplenomegaly, cardiac disease, respiratory disease, and neurodevelopmental involvement. However, Hurler syndrome is IDUA deficiency within MPS I, whereas the IEMbase row is VPS33A-related MPS-plus syndrome.

The Mucopolysaccharidoses grouping currently defines membership around deficiency of a GAG-degrading lysosomal enzyme and lists classic enzyme MPS members. VPS33A MPS-plus is not represented there and may not fit that membership definition cleanly because its primary gene is a vesicle-trafficking / lysosomal pathway component rather than a canonical GAG-degrading enzyme.

Concordance and completeness

Judgement: true local VPS33A MPS-plus gap; reject Hurler as exact.

The weak Hurler candidate is useful as phenotype context but would conflate the gene, enzyme defect, and mechanism. The IEMbase phenotype signal also includes hematologic/bone-marrow, renal proteinuria, severe infection/respiratory, and cardiac-plus features that are central to MPS-plus and not well modeled by a classic MPS I entry.

Curation actions

  • Do not map to Hurler_syndrome.yaml as exact coverage.
  • Curate VPS33A-related mucopolysaccharidosis-plus syndrome separately if selected.
  • Revisit whether the MPS grouping should include or explicitly exclude MPS-plus disorders under a separate rationale.
  • Preserve heparan/dermatan/total GAG, oligosaccharide, coarse facies, hepatosplenomegaly, dysostosis, hematologic, proteinuria, cardiac, respiratory/infection, developmental, pyramidal, and optic-atrophy prompts.