B-mannosidase deficiency

An inherited metabolic disorder affecting the breakdown of mannose-containing oligosaccharides

B-mannosidase deficiency is a rare lysosomal storage disorder characterized by the body's inability to properly break down certain complex carbohydrates known as mannose-containing oligosaccharides. This condition is caused by mutations in the MANBA gene, which encodes the enzyme beta-mannosidase. The deficiency of this enzyme leads to the accumulation of mannose-rich oligosaccharides in the body, resulting in a variety of symptoms.

Genetics

B-mannosidase deficiency is inherited in an autosomal recessive manner. This means that an affected individual must inherit two copies of the mutated gene, one from each parent. The MANBA gene is located on chromosome 4q22-q25. Mutations in this gene disrupt the normal function of the beta-mannosidase enzyme, leading to the accumulation of undigested oligosaccharides.

Symptoms

The symptoms of B-mannosidase deficiency can vary widely among affected individuals. Common symptoms include:

• Developmental delay
• Intellectual disability
• Hearing loss
• Recurrent infections
• Skeletal abnormalities

The severity of symptoms can range from mild to severe, and some individuals may present with additional symptoms such as hypotonia (reduced muscle tone) and ataxia (lack of voluntary coordination of muscle movements).

Diagnosis

Diagnosis of B-mannosidase deficiency typically involves a combination of clinical evaluation, biochemical testing, and genetic testing. Biochemical tests can measure the activity of beta-mannosidase in leukocytes or fibroblasts. Genetic testing can confirm the diagnosis by identifying mutations in the MANBA gene.

Treatment

Currently, there is no cure for B-mannosidase deficiency. Treatment is primarily supportive and symptomatic. Management may include:

• Physical therapy to improve motor skills
• Speech therapy
• Hearing aids for hearing loss
• Regular monitoring and treatment of infections

Research is ongoing to explore potential therapies, including enzyme replacement therapy and gene therapy.

Prognosis

The prognosis for individuals with B-mannosidase deficiency varies depending on the severity of the condition. Early diagnosis and intervention can help manage symptoms and improve quality of life.

Also see

• Lysosomal storage disorder
• Mannose
• Autosomal recessive disorder
• Enzyme replacement therapy