IEMbase 0299: GNPTAB-related UDP-N-acetylglucosamine-1-phosphotransferase subunit alpha/beta deficiency
Scope
| Field | Value |
|---|---|
| IEMbase ID | 299 |
| Nosology | 20.6.01.03 |
| Gene | GNPTAB |
| External IDs | OMIM:252500; ORPHA:576 |
| Generated mapping | MAPPED; Mucolipidosis_Type_II.yaml |
| Candidate DisMech targets | Mucolipidosis_Type_II.yaml |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents mucolipidosis II alpha/beta / I-cell disease due to GNPTAB. Inheritance is autosomal recessive and treatability is unknown.
Clinical rows include coarse facial features, corneal clouding, gingival hypertrophy, hepatosplenomegaly, hernias, hip dislocation, axial hypotonia, intellectual disability, speech disturbance, valvular thickening, cardiomyopathy, foam cells, joint contractures, recurrent otitis media, and psychomotor retardation. IEMbase also has neuroimaging rows for cortical atrophy, subcortical atrophy, CNS hypomyelination, and thin corpus callosum. Biochemical rows show very low fibroblast/RBC enzyme activity, high serum enzyme activity, normal-to-increased urinary glycosaminoglycans, and markedly increased urinary oligosaccharides.
DisMech phenotype coverage
Mucolipidosis_Type_II.yaml is the correct local target. The local entry models
GNPTAB loss, GlcNAc-1-phosphotransferase deficiency, failure of mannose-6-
phosphate lysosomal targeting, hydrolase missorting/hypersecretion, multisystem
lysosomal substrate accumulation, skeletal/connective-tissue disease,
cardiorespiratory storage disease, and neuromotor developmental arrest.
Local phenotypes include coarse facial features, gingival overgrowth, dysostosis multiplex, cardiac valve disease, respiratory insufficiency, growth failure, joint contractures, kyphosis, thickened skin, developmental delay, and autosomal recessive inheritance. Local diagnostic coverage includes plasma lysosomal enzyme activity and GNPTAB sequencing.
Concordance and completeness
Judgement: correct high-concordance mapping to Mucolipidosis_Type_II.yaml.
IEMbase and DisMech agree on GNPTAB identity, recessive inheritance, impaired GlcNAc-1-phosphotransferase/M6P targeting, extracellular enzyme hypersecretion with intracellular lysosomal deficiency, coarse facies, gingival overgrowth, joint contractures, cardiac-valve disease, developmental delay, and severe multisystem storage. DisMech is stronger for causal mechanism and the cardiorespiratory/skeletal pathophysiology chain.
IEMbase adds granular review prompts for hepatosplenomegaly, hernias, hip dislocation, recurrent otitis media, foam cells, speech disturbance, corneal clouding, MRI cortical/subcortical atrophy, hypomyelination, thin corpus callosum, urinary oligosaccharides, urinary GAGs, and the compartment-specific enzyme pattern.
Curation actions
- Keep this record mapped to
Mucolipidosis_Type_II.yaml. - Consider adding the IEMbase compartment-specific enzyme assay pattern and urinary oligosaccharide/GAG rows as diagnostic biochemical prompts.
- Review the neuroimaging, hepatosplenic, otitis, hernia, hip, speech, corneal, and foam-cell rows before importing.