Maroteaux Lamy Syndrome

Maroteaux Lamy Syndrome

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Maroteaux Lamy Syndrome is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • Arylsulfatase-B Deficiency
  • MPS Disorder VI
  • MPS VI
  • Mucopolysaccharidosis VI
  • Polydystrophic Dwarfism

Disorder Subdivisions

  • None

General Discussion

Maroteaux-Lamy syndrome is a rare genetic metabolic disorder that belongs to a group of disorders known the mucopolysaccharidoses. The disorder is also known as mucopolysaccharidosis (MPS) type VI. Maroteaux-Lamy syndrome occurs in three types: a classic severe type, an intermediate type, and a mild type. The syndrome is characterized by a deficiency in the enzyme arylsulfatase B (also called N- acetylgalactosamine-4-sulfatase), which leads to an excess of dermatan sulfate in the urine.



In general, growth retardation occurs from two to three years of age, with coarsening of facial features and abnormalities in the bones of hands and spine. Joint stiffness also occurs. The intellect is usually normal.



The mucopolysaccharidoses (MPS) are a group of inherited lysosomal storage disorders. Lysosomes function as the primary digestive units within cells. Enzymes within lysosomes break down or digest particular nutrients, such as certain carbohydrates and fats. In individuals with MPS disorders, deficiency or malfunction of specific lysosomal enzymes leads to an abnormal accumulation of certain complex carbohydrates (mucopolysaccharides or glycosaminoglycans) in the arteries, skeleton, eyes, joints, ears, skin, and/or teeth. These accumulations may also be found in the respiratory system, liver, spleen, central nervous system, blood, and bone marrow. This accumulation eventually causes progressive damage to cells, tissues, and various organ systems of the body. There are several different types and subtypes of mucopolysaccharidosis. These disorders, with one exception, are inherited as autosomal recessive traits.

Symptoms

The symptoms of Maroteaux-Lamy syndrome vary greatly from case to case. Signs of Maroteaux-Lamy syndrome usually appear between 2 and 3 years of age with the most readily detectable symptoms being coarse facial features such as thick nostrils and lips and development of a dwarf-like appearance.



Bone abnormalities such as large hands with stubby fingers, stiff joints, joint pain, a hunched spine, prominent breastbone (pectus carinatum), and pain in the hipbone all tend to appear after the first three to four years. Also evident at this time may be a wobbly gait, resulting from inwardly pointed knees and toes.



Noisy and strained breathing, intermittent deafness and enlargement of the liver and spleen (hepatosplenomegaly) may also occur. Additional symptoms include hernias, joint contractures, and clouding of the corneas.



Possible complications include blindness, progressive hearing loss, heart abnormalities, muscle weakness, and excessive fluid on the brain (hydrocephalus). (For more information, choose "hydrocephalus" as your search term in the Rare Disease Database.)

Causes

Maroteaux-Lamy syndrome is an autosomal recessive inherited disorder caused by a deficiency of the enzyme arylsulfatase B. This enzyme deficiency leads to the accumulation of certain complex carbohydrates within the body's cells, resulting in progressive cellular, tissue, and organ system dysfunction. The gene associated with the enzyme deficiency is found on the long arm of chromosome 5 (5q11-q13).



Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22, and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome, and females have two X chromosomes. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many numbered bands. For example, "chromosome 5q11-q13" refers to bands 11 to 13 on the long arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome.



Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.



Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, he or she will be a carrier of the disease, but usually will not show symptoms. The risk of two carrier parents both passing the defective gene and having an affected child is 25% with each pregnancy. The risk of having a child who is a carrier, like the parents, is 50% with each pregnancy. The chance of having a child who receives normal genes from both parents and is genetically normal for that particular trait is 25%. The risk is the same for males and females.



All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than do unrelated parents of both carrying the same abnormal gene, which increases the risk of having children with a recessive genetic disorder.

Affected Populations

Maroteaux-Lamy syndrome affects males and females equally. The incidence of this disorder is unknown. The incidence of all forms of mucopolysaccharidosis is estimated to be one in 25,000 births. However, because mucopolysaccharidoses often go unrecognized, these disorders are under-diagnosed or misdiagnosed, making it difficult to determine their true frequency in the general population.

Standard Therapies

The U.S. Food and Drug Administration (FDA) approved the orphan drug Naglazyme for the treatment of Maroteaux Lamy syndrome in June 2005. Naglazyme is the first FDA-approved drug for this condition. For information about this drug, contact the manufacturer:



BioMarin Pharmaceutical, Inc.

105 Digital Drive

Novato, CA 94949

Telephone: (415) 506-6700

Fax: (415) 382-7889



Additional treatment for Maroteaux-Lamy syndrome is symptomatic and supportive. Hernias and joint contractures may be corrected by surgery. Physical therapy and hearing aids may benefit some affected individuals.



Genetic counseling may be helpful to affected individuals and family members. Prenatal diagnosis is now possible for this disorder.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.



For information about clinical trials being conducted at the National Institutes of Health (NIH) Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:



Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov



Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.



For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:



Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com



Since prenatal diagnosis is now possible through amniocentesis and sampling of a tissue layer in the embryo (chorionic villus sampling), new treatments aimed at checking early development of Maroteaux-Lamy syndrome are now under study. Replacing defective enzymes via enzyme replacement therapy and bone marrow transplants are two of the treatment approaches that have been studied. Scientific study of gene replacement in animal models raises the hope that gene replacement may someday be made available to people with genetic disorders such as Maroteaux- Lamy syndrome.



Bone marrow transplantation to treat a young girl with Maroteaux-Lamy syndrome greatly decreased the size of her enlarged liver and spleen, and improved her cardiopulmonary function, joint mobility, and visual acuity. The successful outcome of the bone marrow transplant demonstrates that toxic compounds that accumulate in the tissues can be removed and metabolized by transplanted cells. However, more research is needed before this treatment will be available for general use.

References

MPS Society Brochure.



MPS Research Funding Center Bulletin.



TEXTBOOKS

Clarke JTR. MPS-VI (Maroteaux-Lamy syndrome). In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:559.



Thoene JG., ed. Physicians' Guide to Rare Diseases. Montvale, NJ: Dowden Publishing Company Inc; 1995:211-12.



Scriver CR, et al., eds. The Metabolic and Molecular Basis of Inherited Disease. 7th Ed. New York, NY; McGraw-Hill Companies, Inc; 1995:2467-69.



Andersson HC, Shapira E., The Mucopolysaccharidoses. In: Bennett JC, Plum F., eds. Cecil Textbook of Medicine. 20th ed. Philadelphia, PA: W.B. Saunders Co; 1996:1118-19.



Berkow R., ed. The Merck Manual-Home Edition. Whitehouse Station, NJ: Merck Research Laboratories; 1997:1308.



Beers MH, Berkow R., eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:2407-09.



JOURNAL ARTICLES

Harmatz P, et al., Direct comparison of measures of endurance, mobility, and joint function during enzyme-replacement therapy of mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome): results after 48 weeks in a phase 2 open-label clinical study of recombinant human N-acetylgalactosamine 4-sulfatase. Pediatrics. 2005;115:e681-9.



Harmatz P, et al., Enzyme replacement therapy in mucopolysaccharidosis VI (Maroteaux-Lamy syndrome). J Pediatr. 2004;144:574-80.



Alroy J, et al., Altered corneal stromal matrix organization is associated with mucopolysaccharidosis I, II and VI. Exp Eye Res. 1999:68;523-30.



Herskhovitz E, et al., Bone marrow transplantation for Maroteaux-Lamy syndrome (MPS VI): long-term follow-up. J Inherit Metab Dis. 1999;22:50-62.



Villani GR, et al., Maroteaux-lamy syndrome: five novel mutations and their structural localization. Biochim Biophys Acta. 1999;1453:185-92.



Laver NM, et al., Mild form of Maroteaux-Lamy syndrome: corneal histopathology and ultrastructure. Cornea. 1999;17:664-68.



Alvaro F, et al., Allogenic CD34 selected peripheral stem cell transplant for Maropteaux-Lamy syndrome (mucopolysaccharidosis type VI): rapid haemopoietic and biochemical reconstitution. Bone marrow Transplant. 1998;21:419-21.



Hite SH, et al., Syringomyelia in mucopolysaccharisosis type VI (Maroteaux-Lamy syndrome): imaging findings following bone marrow transplantation. Pediatr Radiol. 1997;27:736-38.



Hachida M, et al., Combined aortic and mitral valve replacement in an adult with mucopolysaccharidosis (Maroteaux-Lamy syndrome). Heart vessels. 1996;11:215-17.



Buyukebiz B, et al., Maroteaux-Lamy syndrome associated with growth hormone deficiency. J Pediatr Endocrinol Metab. 1995;8:305-07.



Frey JB., What dwarfed Toulouse-Lautrec? Nat Genet. 1995;10:128-30.



FROM THE INTERNET

McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No: 253200; Last Update:02/01/2000.

Resources

CLIMB (Children Living with Inherited Metabolic Diseases)

Climb Building

176 Nantwich Road

Crewe, CW2 6BG

United Kingdom

Tel: 4408452412173

Fax: 4408452412174

Email: enquiries@climb.org.uk

Internet: http://www.CLIMB.org.uk



Vaincre Les Maladies Lysosomales

2 Ter Avenue

Massy, 91300

France

Tel: 0169754030

Fax: 0160111583

Email: accueil@vml-asso.org

Internet: http://www.vml-asso.org



Lighthouse International

111 E 59th St

New York, NY 10022-1202

Tel: (800)829-0500

Email: info@lighthouse.org

Internet: http://www.lighthouse.org



National MPS Society, Inc.

PO Box 14686

Durham, NC 27709

Tel: (919)806-0101

Fax: (919)806-2055

Tel: (877)677-1001

Email: info@mpssociety.org

Internet: http://www.mpssociety.org



NIH/National Institute of Diabetes, Digestive & Kidney Diseases

Office of Communications & Public Liaison

Bldg 31, Rm 9A06

31 Center Drive, MSC 2560

Bethesda, MD 20892-2560

Tel: (301)496-3583

Email: NDDIC@info.niddk.nih.gov

Internet: http://www2.niddk.nih.gov/



Society for Mucopolysaccharide Diseases

MPS House

Repton Place

White Lion Road

Amersham

Buckinghamshire, HP7 9LP

United Kingdom

Tel: 08453899901

Fax: 08453899902

Email: mps@mpssociety.co.uk

Internet: http://www.mpssociety.co.uk



Canadian Society for Mucopolysaccharide and Related Diseases, Inc.

PO Box 30034

RPO Parkgate

North Vancouver

British Columbia, V7H 2Y8

Canada

Tel: 6049245130

Fax: 6049245131

Tel: 8006671846

Email: info@mpssociety.ca

Internet: http://www.mpssociety.ca



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



Hide & Seek Foundation for Lysosomal Disease Research

6475 East Pacific Coast Highway Suite 466

Long Beach, CA 90803

Tel: (877)621-1122

Fax: (866)215-8850

Email: info@hideandseek.org

Internet: http://www.hideandseek.org



For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.

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