Beta-mannosidosis

Beta-mannosidosis is a very rare genetic condition that affects the way certain types of sugar molecules are processed by the body. Presentations of the disease can vary significantly, with some experiencing an early onset of symptoms and a rapidly progressive illness, and others experiencing mild symptoms which can present later in childhood or adolescence. It is one of about 50 diseases that are classified as lysosomal storage disorders (LSD), where a genetic variation disrupts the normal activity of lysosomes in human cells.

Lysosomes in human cells contain specific proteins known as enzymes which are responsible for breaking down and recycling molecules such as fats and sugars. Individuals with a lysosomal storage disorder lack one of these necessary enzymes, or do not contain one of these enzymes in sufficient quantities to break down molecules in the way we would expect for proper cellular function.

Children with beta-mannosidosis may present with symptoms shortly after birth, or they may not show signs or symptoms until later in life.

Symptoms may include:

• Intellectual disability
• Delayed motor development
• Seizures
• Clusters of dark, red spots on skin (angiokeratomas)
• Distinctive facial features (coarse facial features)
• Frequent ear infections/respiratory infections
• Hearing loss
• Poor muscle tone (hypotonia)
• Psychiatric and/or behavioral disturbances
• Reduced sensation in the extremities (peripheral neuropathy)

Beta-mannosidosis is caused by mutations in a gene known as MANBA, which provides instructions for the production of an enzyme called beta-mannosidase. This enzyme is located in a cell’s lysosomes and is responsible for the breakdown and recycling of specific complex sugars which contain a sugar molecule called mannose. Genetic mutations in the MANBA gene interfere with the ability of beta-mannosidase to perform its function correctly, leading to an accumulation of complex sugar molecules in cells that eventually causes cells to malfunction. This genetic condition is inherited in an autosomal recessive pattern, which means that an affected child has received one defective copy of the MANBA gene from each of their parents.

At the Boston Children’s Lysosomal Storage Disorders (BoLD) Program, our team of providers is committed to the care of complex patients. As part of Boston Children’s Hospital, we are prepared to meet the challenge of providing multifaceted care by partnering with you and your child to deliver direct care in our BoLD clinic. We work with the broad array of world-class specialists at Boston Children’s to optimize the care we provide your child with beta-mannosidosis.