Beta-mannosidosis

A rare genetic disorder affecting glycoprotein metabolism

Beta-mannosidosis is a rare lysosomal storage disorder caused by a deficiency of the enzyme beta-mannosidase. This enzyme deficiency leads to the accumulation of mannose-containing oligosaccharides in the body, resulting in a variety of clinical symptoms.

Pathophysiology

Beta-mannosidosis is an autosomal recessive disorder, meaning that an individual must inherit two copies of the defective gene, one from each parent, to manifest the disease. The condition is caused by mutations in the MANBA gene, which encodes the enzyme beta-mannosidase. This enzyme is responsible for breaking down complex sugars in the lysosome, a cellular organelle involved in the degradation of macromolecules.

In individuals with beta-mannosidosis, the lack of functional beta-mannosidase leads to the accumulation of mannose-rich oligosaccharides in various tissues, including the central nervous system, kidneys, and liver. This accumulation disrupts normal cellular function and leads to the clinical manifestations of the disease.

Clinical Features

The symptoms of beta-mannosidosis can vary widely among affected individuals, but common features include:

• Intellectual disability
• Hearing loss
• Speech delay
• Motor dysfunction
• Recurrent infections
• Skeletal abnormalities

The severity of symptoms can range from mild to severe, and the age of onset can vary from infancy to adulthood.

Diagnosis

Diagnosis of beta-mannosidosis is typically based on clinical evaluation, biochemical testing, and genetic analysis. Biochemical testing involves measuring 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 beta-mannosidosis, and treatment is primarily supportive and symptomatic. Management may include:

• Physical therapy and occupational therapy to improve motor skills
• Speech therapy to address communication difficulties
• Hearing aids or other interventions for hearing loss
• Regular monitoring and treatment of infections

Research into potential therapies, such as enzyme replacement therapy and gene therapy, is ongoing.

Prognosis

The prognosis for individuals with beta-mannosidosis varies depending on the severity of the condition. Some individuals may lead relatively normal lives with appropriate supportive care, while others may experience significant disability.

Related pages

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