Alpha-Mannosidosis

Alpha-Mannosidosis – Treatment Overview

Introduction
Alpha-mannosidosis is a rare, progressive lysosomal storage disorder caused by deficiency of the enzyme alpha-D-mannosidase. This enzyme normally breaks down mannose-rich oligosaccharides; its deficiency results in accumulation of these sugars in cells and tissues. The condition is inherited in an autosomal recessive manner. Clinical manifestations include:

• Recurrent infections due to immune dysfunction

• Hearing loss

• Skeletal abnormalities (dysostosis multiplex)

• Intellectual disability and developmental delay

• Muscle weakness and ataxia

The disease course ranges from mild to severe. Management focuses on enzyme replacement therapy (ERT) where available, hematopoietic stem cell transplantation (HSCT) in selected cases, and supportive treatment to improve quality of life.

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Treatment Options and Doses

1. Enzyme Replacement Therapy (ERT)

• Velmanase alfa (Lamzede®) – the first approved therapy for non-neurological manifestations of alpha-mannosidosis.

  • Dose (adults and children ≥6 years): 1 mg/kg IV once weekly.

  • Administered as an intravenous infusion over ~50 minutes.

  • Benefits: Improves immune function, reduces infection rate, improves endurance, and decreases mannose-rich oligosaccharide storage.

  • Does not significantly cross the blood-brain barrier → limited effect on cognitive decline.

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2. Hematopoietic Stem Cell Transplantation (HSCT)

• Considered in severe early-onset cases or where ERT is not available.

• HSCT can restore enzyme activity from donor cells, stabilizing or improving neurological and somatic symptoms.

• Risks include transplant-related morbidity and mortality, so it is usually offered in specialized centers.

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3. Supportive and Symptomatic Treatment

• Hearing loss: Hearing aids or cochlear implants.

• Musculoskeletal complications: Orthopedic surgery or physiotherapy for joint deformities and muscle weakness.

• Infections: Prophylactic antibiotics, prompt treatment of respiratory infections.

• Neurological/psychological support: Speech therapy, occupational therapy, and educational interventions.

• Seizures (if present): Antiepileptic drugs tailored to seizure type.

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4. Monitoring and Long-Term Care

• Regular assessments of:

  • Pulmonary function

  • Cardiac status (ECG, echocardiography)

  • Hearing and vision

  • Neurocognitive development

• Multidisciplinary care team: genetics, neurology, orthopedics, ENT, physiotherapy, and psychology.