Alpha-mannosidosis

Alpha-mannosidosis is a rare lysosomal storage disorder caused by deficiency of the enzyme alpha-mannosidase, which is essential for the breakdown of complex sugar molecules (oligosaccharides) within cells. The disease is caused by pathogenic variants in the MAN2B1 gene located on chromosome 19. When alpha-mannosidase is deficient, mannose-rich oligosaccharides accumulate in lysosomes throughout the body, leading to progressive cellular damage affecting multiple organ systems. The condition is also known as lysosomal alpha-mannosidase deficiency. Clinical features are highly variable but typically include intellectual disability, skeletal abnormalities (dysostosis multiplex), coarsened facial features, hearing impairment, recurrent infections due to immune deficiency, and hepatosplenomegaly. The disease has historically been classified into a severe infantile form (type I) with rapid progression and early death, and a milder juvenile/adult form (type II) with slower progression and survival into adulthood, though the clinical spectrum is now recognized as a continuum. Additional features may include ataxia, psychiatric symptoms, and myopathy, which can become more prominent with age. Treatment options include enzyme replacement therapy (ERT) with velmanase alfa (Lamzede), which was approved in the European Union in 2018 for non-neurological manifestations of the disease. Hematopoietic stem cell transplantation (HSCT) has been used in some patients, particularly younger children, and may provide benefit if performed early in the disease course. Supportive care including hearing aids, educational support, physical therapy, and management of infections remains an important component of treatment. Early diagnosis and intervention are critical for optimizing outcomes.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Alpha-mannosidosis