Mucolipidosis III alpha/beta (Pseudo-Hurler Polydystrophy)
Mucolipidosis III alpha/beta results from a deficiency of the enzyme N-acetylglucosamine-1-phosphotransferase. Just as luggage in an airport is tagged to direct it to the correct destination, enzymes are often "tagged". In Mucolipidosis III alpha/beta, the deficient enzyme is supposed to tag other enzymes (activator proteins) so that they can initiate certain metabolic processes in the cell. Because the activator proteins are not properly tagged, they escape into spaces outside the cell and therefore cannot do their usual work of breaking down substances inside the cells.
Mucolipidosis III alpha/beta is a slowly progressive disorder that affects many parts of the body. Signs and symptoms of this condition typically appear around age 3 or 4, but some children are not diagnosed until later on in life.
Individuals with mucolipidosis III alpha/beta grow slowly and have short stature. They also have stiff joints and dysostosis multiplex, which refers to multiple skeletal abnormalities seen on x-ray. Many affected individuals develop low bone mineral density (osteoporosis), which weakens the bones and makes them prone to fracture. Osteoporosis and progressive joint problems also cause bone pain that becomes more severe over time in people with mucolipidosis III alpha/beta.
Management. Treatment of manifestations: Low-impact physical therapy is usually well tolerated. Myringotomy tube placement should be used with caution in the treatment of recurrent ear infections. Carpal tunnel signs may require tendon release. In late childhood or early adolescence relief of hip pain following exercise becomes important; in older adolescents and adults with milder phenotypic variants, bilateral hip replacement has been successful. Later in the disease course management focuses on relief of general bone pain associated with osteoporosis, which has responded in a few individuals to monthly IV administration of the bisphosphonate pamidronate.
Prevention of secondary complications: Because of concerns about airway management, surgical intervention should be undertaken only in tertiary care settings with pediatric anesthesiologists.
How common is Mucolipidosis type III alpha/beta
Mucolipidosis III alpha/beta is a rare disorder, although its exact prevalence is unknown. It is estimated to occur in about 1 in 100,000 to 400,000 individuals worldwide.
At present there is no therapy for Mucolipidosis III alpha/beta. Many of the complications can be well managed by surgical procedures. Secondary Metabolic bone disease can be well managed with Pamidronate. See medical papers below.
Medical and Research Information
- GeneReviews: Gives good descriptions of genetic diseases. Information is comprehensive, and access is free to all users.
- Genetics Home Reference: This has an excellent description of Mucolipidosis III alpha/beta with good reference to other information and resources.
- GeneTests: A list of laboratories testing for Mucolipidosis.
- Clinical Trials: A registry of federally and privately supported clinical trials conducted in the United States and around the world. This site gives you information about the trial's purpose, who may participate and the locations
- Orphanet: A database dedicated to information on rare diseases and orphan drugs. Access is free of charge.
- OMIM: Has technical information about the genetics of this disorder . It is a site developed for scientists and medical specialists and contains both general and highly technical information. Access to this site is free.
- Genetic and Rare Diseases Information Center (GARD): A collaborative effort of two agencies of the National Institutes of Health, The Office of Rare Diseases Research (ORDR) and the National Human Genome Research Institute (NHGRI) to help people find useful information about genetic conditions and rare diseases.
- The natural history and osteodystrophy of mucolipidosis types II and III
- The osteodystrophy of mucolipidosis type III and the effects of intravenous pamidronate treatment
- Pamidronate infusion guidelines for mucolipidosis
- Molecular order in Mucolipidosis II and III Nomenclature
- Additional papers can be found here.
Patient Support groups
- ISMRD: The International Advocate for Glycoprotein Storage Diseases
- ISMRD’s Facebook page; this is a closed group and is for families only
- ISMRD’s public Facebook Page.
- LDNZ: Lysosomal Diseases New Zealand is the support group for families in New Zealand
- Various MPS societies around the world also support Mucolipidosis III