Beta-mannosidosis

Beta-mannosidosis is an extremely rare lysosomal storage disorder caused by a deficiency of the enzyme beta-mannosidase, which is essential for the sequential degradation of N-linked glycoproteins. This deficiency leads to the accumulation of the disaccharide mannosyl-beta(1,4)-N-acetylglucosamine and other oligosaccharides in tissues and body fluids. The disease is caused by pathogenic variants in the MANBA gene located on chromosome 4q24. Beta-mannosidosis primarily affects the central nervous system, immune system, and connective tissues. Clinical presentation is highly variable, even among affected individuals within the same family. The most commonly reported features include intellectual disability (ranging from mild to severe), hearing loss, recurrent infections, behavioral abnormalities (including hyperactivity and aggression), speech impairment, and facial dysmorphism. Some patients may also exhibit angiokeratomas (skin lesions), skeletal abnormalities, and hypotonia. Neurological involvement is a hallmark of the condition, with developmental delay often being the presenting concern in childhood. A few severely affected individuals have presented in the neonatal period with more profound neurological impairment. There is currently no specific or curative treatment for beta-mannosidosis. Management is supportive and symptomatic, focusing on educational support, speech therapy, management of behavioral issues, hearing aids for hearing loss, and treatment of recurrent infections. Enzyme replacement therapy and substrate reduction therapy have not been developed for this condition. Fewer than 30 cases have been reported in the medical literature worldwide, making it one of the rarest lysosomal storage disorders. Genetic counseling is recommended for affected families.

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