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What

Alpha-Mannosidosis is a rare genetic disorder that usually manifests with mental retardation, hearing impairment, various bone changes, and recurrent infections. It is a part of a larger group of disorders known as the lysosomal storage diseases.

Who

The frequency of alpha-mannosidosis is estimated to be close to 1 in every 500,000 people. Males and females are equally affected and there is no racial preference.

Signs and Symptoms

In general, the presentation is highly variable in children with alpha-mannosidosis. They may exhibit the following:

• Unique coarse facial features with prominent forehead, flattened nasal bridge, big tongue, wide-spaced teeth.
  
• Mental retardation with delayed speech
  
• Loss of balance and coordination
  
• Skeletal anomalies: weakened bones, deformed back, knock-knees
  
• Hearing loss
  
• Repeated infections from a weakened immune system
  
• Vision changes with blurring and mal-alignment.
  
• Enlarged liver and spleen.

Possible Causes

The cause of alpha-mannosidosis has been linked to mutations in a gene known as MAN2B1. Defects in this gene results in lowered production of a protein called lysosomal alpha-mannosidase that plays an important role in removing harmful waste products at the cellular level. When these wastes accumulate in the body, the brain and other organs do not develop properly. Alpha-mannosidosis is inherited through an autosomal recessive manner, thus a child will need two copies of the defective MAN2B1 gene to be affected. Some forms of alpha-mannosidosis are very severe, and show up in infancy, with a high risk of death from infection. Others are mild, and infections are not such a problem. These children generally live much longer, and the skeletal and hearing problems are the main problems for them.

Diagnosis

Making the diagnosis of alpha-mannosidosis depends upon linking the characteristic facial features, skeletal defects, and neurologic deficits with specific blood tests. The confirmatory test measures the amount of alpha-mannosidase in the blood. Genetic and biochemical tests from the blood can determine the type of alpha-mannosidosis a patient has. Your doctor may also obtain imaging studies such as an MRI (magnetic resonance image) to evaluate the brain.

Treatment

The management of children with alpha-mannosidosis requires close monitoring of disease progression, symptomatic care, and offering families experimental treatments such as bone marrow transplant and enzyme therapy. Monitoring should include: eye exams, hearing tests, neuropsychological testing, x-rays, and MRI of the brain if warranted. When performed early, bone marrow transplantation can potentially cure patients, however it is not without significant risk of infection and permanent disability. enzyme replacement and gene therapy are currently only experimental.

Prognosis

Children with alpha-mannosidosis have variable courses of their disease depending on the specific type identified. In the severe form there is a high risk of early death. In other forms, children may live into their 50s.

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.

Weblinks

Alpha Mannosidosis
Useful general information for parents and professionals.

Gene Reviews
Nice, concise summary of relevant findings and genetic testing and counseling options.

International Society of Mannosidosis
bone marrow transplant information for families who are interested.

Google Search for Alpha-Mannosidosis

References and Sources

Riise. HMF. et al. (1999) Characterization of a novel alpha-mannosidosis-causing mutation and its use in leukocyte genotyping after bone marrow transplantation. Hum Genet 104:106-107. Berg, T. et al. (1999) Spectrum of Mutations in alpha-Mannosidosis. Am. J. Hum. Genet. 64:77-88.