Alpha-Mannosidosis is caused by deficient activity of the enzyme alpha-D-mannosidase. There are three clinical subtypes, which include: • Type 1: a mild form recognized after age ten years with absence of skeletal abnormalities, myopathy, and slow progression. • Type 2: a moderate form recognized before age ten years with presence of skeletal abnormalities, myopathy, and slow progression. • Type 3: a severe form manifested as prenatal loss or early death from progressive central nervous system involvement. The disease causes a diffuse dysfunction of the brain, with a mixture of strong and weak mental performances. Recurrent infections is a main feature of the disease.

Symptoms range widely in their onset and severity. Often the appearance of an affected individual includes: Intellectual disability; distinctive facial features; and skeletal abnormalities such as reduced bone density (osteopenia), thickening of the bones at the top of the skull (calvaria), deformations of the bones in the spine (vertebrae), bowed legs or knock knees, and deterioration of the bones and joints. Characteristic facial features include a large head, prominent forehead, low hairline, rounded eyebrows, large ears, flattened bridge of the nose, protruding jaw, widely spaced teeth, overgrown gums, and large tongue. Affected individuals may also experience difficulty in coordinating movements (ataxia); muscle weakness (myopathy); delay in developing motor skills such as sitting and walking; speech impairments; increased risk of infections; enlargement of the liver and spleen (hepatosplenomegaly); a buildup of fluid in the brain (hydrocephalus); hearing loss; a clouding of the lens of the eye (cataract); and psychiatric symptoms such as depression, anxiety, or hallucinations. Immune-Deficiency: Recurrent infections is a main feature of the disease. These infections are in the upper or lower respiratory tract, in the middle ear, or in the gastrointestinal tract. Skeletal Problems: The skeletal malformation is especially seen in the spine of the chest which may give the patients a rigid and deformed spine and back pain. Further, a less acknowledged complication of the disease is the destruction of the joints.

Alpha-Mannosidosis is caused by deficient activity of the enzyme alpha-D-mannosidase.

Diagnosis is based on identifying characteristic symptoms, detailed patient history, and clinical evaluation. Confirmation is typically done through enzyme assays showing deficient alpha-D-mannosidase activity and molecular genetic testing.

Bone marrow/ stem cell transplant: There have been a number of children who have had this treatment. ISMRD is currently funding research into the long-term effects of bone marrow transplant for Alpha-Mannosidosis. Enzyme replacement therapy: partially approved in Europe (2018) and America (2023). It involves replacing the missing enzyme to help break down the accumulated materials.