Beta-mannosidosis (β-mannosidosis) is an extremely rare genetic disease that belongs to a larger group of lysosomal storage disorders. Changes in the MANBA gene cause metabolic abnormality, specifically a loss of a functional β-Mannosidase enzyme, that helps break down complex sugar molecules (oligosaccharides). This results in the buildup of toxic materials in the cells throughout the body and brain.

Severity and progression of the disease vary widely in individuals and symptoms can appear in infancy through adulthood. Most affected individuals experience some degree of intellectual disability and delayed motor development. Other signs and symptoms include speech, swallowing, and hearing difficulties, repeat infections, seizures, gross and fine motor delay, low muscle tone, scoliosis, nystagmus, white matter changes to the brain (leukoencephalopathy), reduced sensations in extremities, dark red spots on the skin (angiokeratomas) and behavioral and psychiatric challenges.

Changes in the MANBA gene cause metabolic abnormality, specifically a loss of a functional β-Mannosidase enzyme.

Diagnosis is difficult due to rarity. It typically involves clinical evaluation, identifying broad symptoms, and is confirmed via enzyme assays (deficiency of beta-mannosidase) and genetic testing (MANBA gene).

Treatment is symptomatic and supportive. The Lost Enzyme Project is conducting preclinical studies necessary for the development of an enzyme replacement therapy for Beta-mannosidosis.