Overview
MAN2B1 encodes lysosomal alpha-mannosidase, an enzyme that plays a crucial role in the breakdown of glycoproteins in lysosomes. The enzyme cleaves mannose residues from oligosaccharides. Mutations in MAN2B1 lead to alpha-mannosidosis, a rare lysosomal storage disease in which oligosaccharides accumulate in cells.
19p13.13 (Chromosome 19)
Hereditary Diseases
Autosomal recessive
~1:500,000 (very rare)
Function & Significance
Lysosomal alpha-mannosidase is an exoglycosidase enzyme located in lysosomes. It catalyzes the hydrolysis of terminal alpha-D-mannose residues of glycoproteins and glycolipids. This degradation is part of the normal recycling of glycoproteins in the cell.
In mutations in MAN2B1, enzyme activity is reduced or completely absent. This leads to the accumulation of mannose-rich oligosaccharides in lysosomes, causing cell damage and the clinical manifestations of alpha-mannosidosis.
🔬 Lysosomal Storage Diseases
Alpha-mannosidosis belongs to the group of lysosomal storage diseases caused by defective lysosomal enzymes. Other examples include Gaucher disease, Fabry disease, and mucopolysaccharidoses. Enzyme replacement therapies are now available for many of these diseases.
Associated Diseases
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🧠 Alpha-Mannosidosis
Progressive intellectual disability, skeletal anomalies, hearing loss, immunodeficiency, coarse facial features
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🦴 Skeletal Dysplasia
Kyphoscoliosis, joint stiffness, short stature
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🛡️ Immunodeficiency
Increased susceptibility to infections, especially respiratory tract infections
🧬 Relevant SNPs
Over 100 different mutations in MAN2B1 have been described. Most are private mutations. Common mutation types include missense, nonsense, frameshift, and splice-site mutations. There is no single common mutation.
⚕️ Clinical Significance & Therapy
Diagnosis: Reduced alpha-mannosidase activity in leukocytes or fibroblasts. Elevated oligosaccharides in urine. Genetic tests confirm MAN2B1 mutations.
Enzyme Replacement Therapy: Velmanase alfa (Lamzede®) has been approved in Europe since 2018. Weekly intravenous infusions can improve symptoms and increase quality of life. Therapy is most effective when started early.
Additional Measures:
- Physiotherapy: For joint stiffness and mobility
- Hearing Aids: For hearing loss
- Avoid Immunosuppression: Infection prophylaxis
- Regular Monitoring: Heart, lungs, skeleton
Prognose: Significantly improved with enzyme replacement therapy. Without therapy, progressive deterioration with reduced life expectancy.
📚 Data Sources
The information on this page is based on the following scientific sources:
- OMIM: #248500 (Mannosidosis, Alpha B, Lysosomal)
- ClinVar: Pathogenic MAN2B1 variants
- PubMed: Literature on alpha-mannosidosis
- Orphanet: ORPHA61 (Alpha-mannosidosis)
- EMA: Velmanase alfa (Lamzede®) Summary of Product Characteristics
Last Update: February 2026