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Genetics Home Reference: your guide to understanding genetic conditions
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Mucolipidosis III alpha/beta

Reviewed October 2014

What is mucolipidosis III alpha/beta?

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.

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.

People with mucolipidosis III alpha/beta often have heart valve abnormalities and mild clouding of the clear covering of the eye (cornea). Their facial features become slightly thickened or "coarse" over time. Affected individuals may also develop frequent ear and respiratory infections. About half of people with this condition have mild intellectual disability or learning problems. Individuals with mucolipidosis III alpha/beta generally survive into adulthood, but they may have a shortened lifespan.

How common is mucolipidosis 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.

What genes are related to mucolipidosis III alpha/beta?

Mutations in the GNPTAB gene cause mucolipidosis III alpha/beta. This gene provides instructions for making a part (subunit) of an enzyme called GlcNAc-1-phosphotransferase. This enzyme helps prepare certain newly made enzymes for transport to lysosomes. Lysosomes are compartments within the cell that use digestive enzymes to break down large molecules into smaller ones that can be reused by cells. GlcNAc-1-phosphotransferase is involved in the process of attaching a molecule called mannose-6-phosphate (M6P) to specific digestive enzymes. Just as luggage is tagged at the airport to direct it to the correct destination, enzymes are often "tagged" after they are made so they get to where they are needed in the cell. M6P acts as a tag that indicates a digestive enzyme should be transported to the lysosome.

Mutations in the GNPTAB gene that cause mucolipidosis III alpha/beta result in reduced activity of GlcNAc-1-phosphotransferase. These mutations disrupt the tagging of digestive enzymes with M6P, which prevents many enzymes from reaching the lysosomes. Digestive enzymes that do not receive the M6P tag end up outside the cell, where they have increased activity. The shortage of digestive enzymes within lysosomes causes large molecules to accumulate there. Conditions that cause molecules to build up inside lysosomes, including mucolipidosis III alpha/beta, are called lysosomal storage disorders. The signs and symptoms of mucolipidosis III alpha/beta are most likely due to the shortage of digestive enzymes inside lysosomes and the effects these enzymes have outside the cell.

Mutations in the GNPTAB gene can also cause a similar but more severe disorder called mucolipidosis II alpha/beta. These mutations completely eliminate the function of GlcNAc-1-phosphotransferase. Mucolipidosis III alpha/beta and mucolipidosis II alpha/beta represent two ends of a spectrum of disease severity.

Related Gene(s)

Changes in this gene are associated with mucolipidosis III alpha/beta.

  • GNPTAB

How do people inherit mucolipidosis III alpha/beta?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of mucolipidosis III alpha/beta?

These resources address the diagnosis or management of mucolipidosis III alpha/beta and may include treatment providers.

  • Gene Review: Mucolipidosis III Alpha/Beta (http://www.ncbi.nlm.nih.gov/books/NBK1875)
  • Genetic Testing Registry: Pseudo-Hurler polydystrophy (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0033788)
  • MedlinePlus Encyclopedia: Cloudy Cornea (http://www.nlm.nih.gov/medlineplus/ency/article/003317.htm)
  • MedlinePlus Encyclopedia: Heart Valves (http://www.nlm.nih.gov/medlineplus/ency/imagepages/9380.htm)

You might also find information on the diagnosis or management of mucolipidosis III alpha/beta in Educational resources (http://www.ghr.nlm.nih.gov/condition/mucolipidosis-iii-alpha-beta/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/mucolipidosis-iii-alpha-beta/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about mucolipidosis III alpha/beta?

You may find the following resources about mucolipidosis III alpha/beta helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for mucolipidosis III alpha/beta?

  • ML III
  • ML IIIA
  • mucolipidosis III
  • mucolipidosis IIIA
  • mucolipidosis III, variant
  • pseudo-Hurler polydystrophy

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about mucolipidosis III alpha/beta?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding mucolipidosis III alpha/beta?

autosomal ; autosomal recessive ; bone mineral density ; cell ; cornea ; digestive ; disability ; enzyme ; gene ; heart valve ; inherited ; joint ; lysosome ; mannose ; mineral ; molecule ; osteoporosis ; phosphate ; prevalence ; recessive ; respiratory ; short stature ; spectrum ; stature ; subunit

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Bargal R, Zeigler M, Abu-Libdeh B, Zuri V, Mandel H, Ben Neriah Z, Stewart F, Elcioglu N, Hindi T, Le Merrer M, Bach G, Raas-Rothschild A. When Mucolipidosis III meets Mucolipidosis II: GNPTA gene mutations in 24 patients. Mol Genet Metab. 2006 Aug;88(4):359-63. Epub 2006 Apr 21. Erratum in: Mol Genet Metab. 2007 Jul;91(3):299. (http://www.ncbi.nlm.nih.gov/pubmed/16630736?dopt=Abstract)
  • Cathey SS, Kudo M, Tiede S, Raas-Rothschild A, Braulke T, Beck M, Taylor HA, Canfield WM, Leroy JG, Neufeld EF, McKusick VA. Molecular order in mucolipidosis II and III nomenclature. Am J Med Genet A. 2008 Feb 15;146A(4):512-3. doi: 10.1002/ajmg.a.32193. (http://www.ncbi.nlm.nih.gov/pubmed/18203164?dopt=Abstract)
  • Cathey SS, Leroy JG, Wood T, Eaves K, Simensen RJ, Kudo M, Stevenson RE, Friez MJ. Phenotype and genotype in mucolipidoses II and III alpha/beta: a study of 61 probands. J Med Genet. 2010 Jan;47(1):38-48. doi: 10.1136/jmg.2009.067736. Epub 2009 Jul 16. (http://www.ncbi.nlm.nih.gov/pubmed/19617216?dopt=Abstract)
  • Gene Review: Mucolipidosis III Alpha/Beta (http://www.ncbi.nlm.nih.gov/books/NBK1875)
  • Kudo M, Brem MS, Canfield WM. Mucolipidosis II (I-cell disease) and mucolipidosis IIIA (classical pseudo-hurler polydystrophy) are caused by mutations in the GlcNAc-phosphotransferase alpha / beta -subunits precursor gene. Am J Hum Genet. 2006 Mar;78(3):451-63. Epub 2006 Jan 24. (http://www.ncbi.nlm.nih.gov/pubmed/16465621?dopt=Abstract)
  • Otomo T, Muramatsu T, Yorifuji T, Okuyama T, Nakabayashi H, Fukao T, Ohura T, Yoshino M, Tanaka A, Okamoto N, Inui K, Ozono K, Sakai N. Mucolipidosis II and III alpha/beta: mutation analysis of 40 Japanese patients showed genotype-phenotype correlation. J Hum Genet. 2009 Mar;54(3):145-51. doi: 10.1038/jhg.2009.3. Epub 2009 Feb 6. (http://www.ncbi.nlm.nih.gov/pubmed/19197337?dopt=Abstract)
  • Steet RA, Hullin R, Kudo M, Martinelli M, Bosshard NU, Schaffner T, Kornfeld S, Steinmann B. A splicing mutation in the alpha/beta GlcNAc-1-phosphotransferase gene results in an adult onset form of mucolipidosis III associated with sensory neuropathy and cardiomyopathy. Am J Med Genet A. 2005 Feb 1;132(4):369-75. (http://www.ncbi.nlm.nih.gov/pubmed/15633164?dopt=Abstract)
  • Tiede S, Muschol N, Reutter G, Cantz M, Ullrich K, Braulke T. Missense mutations in N-acetylglucosamine-1-phosphotransferase alpha/beta subunit gene in a patient with mucolipidosis III and a mild clinical phenotype. Am J Med Genet A. 2005 Sep 1;137A(3):235-40. (http://www.ncbi.nlm.nih.gov/pubmed/16094673?dopt=Abstract)
  • Tylki-Szymańska A, Czartoryska B, Groener JE, Ługowska A. Clinical variability in mucolipidosis III (pseudo-Hurler polydystrophy). Am J Med Genet. 2002 Mar 15;108(3):214-8. (http://www.ncbi.nlm.nih.gov/pubmed/11891688?dopt=Abstract)
  • van Meel E, Qian Y, Kornfeld SA. Mislocalization of phosphotransferase as a cause of mucolipidosis III αβ. Proc Natl Acad Sci U S A. 2014 Mar 4;111(9):3532-7. doi: 10.1073/pnas.1401417111. Epub 2014 Feb 18. (http://www.ncbi.nlm.nih.gov/pubmed/24550498?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: October 2014
Published: October 20, 2014