Beta-mannosidase

Beta-mannosidase is an enzyme that plays a crucial role in the lysosomal degradation of N-linked glycoproteins. It is involved in the breakdown of complex sugars into simpler molecules, specifically by hydrolyzing the terminal, non-reducing beta-D-mannose residues in beta-D-mannosides. This enzyme is encoded by the MANBA gene in humans.

Function

Beta-mannosidase operates within the lysosome, a specialized organelle in the cell that breaks down waste materials and cellular debris. The enzyme's primary function is to degrade oligosaccharides produced during the catabolism of glycoproteins. This process is essential for the normal turnover of cellular components and for the prevention of accumulation of undegraded molecules, which can lead to cellular dysfunction and disease.

Clinical Significance

Deficiency in beta-mannosidase activity is associated with beta-mannosidosis, a rare lysosomal storage disorder. Beta-mannosidosis is characterized by a wide range of clinical manifestations, including intellectual disability, hearing loss, skeletal abnormalities, and recurrent infections. The severity of symptoms can vary significantly among affected individuals. The disorder is inherited in an autosomal recessive manner, meaning that two copies of the defective gene, one from each parent, are required for a child to be affected.

Genetic

The MANBA gene, located on chromosome 4q22-q25, encodes the beta-mannosidase enzyme. Mutations in this gene can lead to reduced or absent enzyme activity, resulting in the accumulation of mannose-rich oligosaccharides in the lysosome and the subsequent development of beta-mannosidosis.

Diagnosis

Diagnosis of beta-mannosidosis typically involves biochemical assays to measure enzyme activity in leukocytes or fibroblasts. Genetic testing can also be used to identify mutations in the MANBA gene. Early diagnosis is important for the management of symptoms and for genetic counseling.

Treatment

There is currently no cure for beta-mannosidosis. Treatment is symptomatic and supportive, focusing on managing the symptoms and improving the quality of life for affected individuals. This may include physical therapy, educational support, and interventions to address hearing and vision impairments. Research into enzyme replacement therapy and other potential treatments is ongoing.

See Also

• Lysosomal storage disorder
• Glycoprotein
• Enzyme

External Links

• MANBA gene on NCBI
• Beta-mannosidosis on Genetics Home Reference