What is Alpha-mannosidosis?
Alpha-mannosidosis is a rare lysosomal storage disorder, which are metabolic diseases that feature an abnormal buildup of toxic materials in the body’s cells because of enzyme deficiencies. It is a progressive disorder, which means that symptoms get worse over time, but symptom presence and severity vary widely from person to person. It is estimated to occur in about 1 in 500,000 people worldwide and affects males and females equally.
There are three different subtypes of Alpha-mannosidosis that depend on the severity of symptoms:
- Type 1: Mild form that appears after age 10, progresses slowly, and does not show skeletal abnormalities or muscle problems.
- Type 2: Moderate form that appears before age 10, progresses slowly, and does show skeletal abnormalities and muscle problems. The most common form.
- Type 3: Severe form that can lead to early death or death before birth because of progressive central nervous system involvement or infection. Usually appears within the first year of life, and symptoms worsen rapidly.
What are the symptoms of Alpha-mannosidosis?
Symptoms can range from mild to severe and often vary, meaning that not all individuals will show every symptom listed below. They include:
- Intellectual disability
- Delayed motor skill development
- Coarse facial features, such as large head, prominent forehead, low hairline, large ears, flattened bridge of the nose, protruding jaw, widely spaced teeth, overgrown gums, large tongue, and rounded eyebrows
- Initial accelerated growth rates that eventually becomes impaired as child ages
- Skeletal abnormalities like reduced bone density, thickened bones at the top of the skull, deformed vertebrae, bowed legs, and deteriorating bones and joints
- Buildup of fluid in the brain (hydrocephalus)
- Hearing loss
- Weakened immune system that increases risk of infection
- Difficulty coordinating movement
- Muscle weakness
- Speech impairments
- Development of cataracts over the eyes
- Depression, confusion, and/or anxiety
What causes Alpha-mannosidosis?
Human traits are inherited from a person’s father and mother; each one contributes a copy of a gene, which interacts with the other copy. Alpha-mannosidosis is inherited in an autosomal recessive pattern, which means that both parents need to pass down a copy of the mutated gene for the condition to occur.
Alpha-mannosidosis occurs when the MAN2B1 gene mutates. This gene helps create a specific type of enzyme (alpha-mannosidase), which works to break down proteins into smaller pieces. Without enough of this enzyme, the proteins build up to toxic levels in the body’s cells, which leads to tissue and organ damage, and then to symptoms.
How is Alpha-mannosidosis diagnosed?
Alpha-mannosidosis can be diagnosed using the following procedures:
- Identifying characteristic findings
- Thorough clinical evaluation
- Detailed patient history
- Specialized tests that notice deficient levels of the enzyme alpha-mannosidase
- Genetic testing
- CT or MRI scans finding excess fluid in the brain
- During pregnancy, amniocentesis and chorionic villus sampling can be used
What are the treatments for Alpha-mannosidosis?
Alpha-mannosidosis treatment works to avoid complications and improve quality of life. It includes:
- Hearing aids
- Surgery to treat skeletal abnormalities
- In the case of hydrocephalus, insertion of a tube, or shunt, to drain excess fluid from the brain
- Bone marrow transplant
- Enzyme replacement
- Special education
- Speech therapy
- Genetic counseling