Alpha-mannosidosis

What is alpha-mannosidosis?

Alpha-mannosidosis is a rare genetic condition characterized by an inability to properly break down certain groups of complex sugars in the body’s cells. The accumulation of sugars affects many of the body’s organs and systems, including the central nervous system. The effects of the disease can vary significantly. While some children may have severe, rapidly progressive illness, others have very few symptoms that are mild in nature. Alpha-mannosidosis is one of about 50 diseases classified as lysosomal storage disorders (LSD), where a genetic variation disrupts the normal activity of lysosomes in human cells.

What are lysosomes and what do they do?

Lysosomes in human cells contain specific proteins known as enzymes that 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 for cells to function properly.

What causes alpha-mannosidosis in children?

Alpha-mannosidosis is caused by mutations in a gene known as MAN2B1, which provides instructions for the production of an enzyme called alpha-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 MAN2B1 gene interfere with the ability of alpha-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 MAN2B1 gene from each of their parents.

What are the symptoms of alpha-mannosidosis?

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

Symptoms may include:

  • characteristic facial features (large head, low hairline, prominent forehead)
  • excessive growth of the gums
  • enlarged tongue
  • skeletal abnormalities
  • immune deficiency
  • difficulty coordinating movements
  • muscle weakness
  • delay in motor skills development
  • speech impairments
  • frequent infections
  • enlarged liver and spleen
  • hearing loss
  • cataracts
  • psychiatric disturbances

How we care for alpha-mannosidosis

At the Boston Children’s Lysosomal Storage Disorder (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 alpha-mannosidosis.