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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.
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.)
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.
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.
There are many types of mucopolysaccharidoses. For more information about each of these disorders, choose "MPS Disorder" as your search term in the Rare Disease Database.
Scheie syndrome (mucopolysaccharidosis type I-S; MPS 1-S) is the mildest form of mucopolysaccharidosis. As in Hurler syndrome, individuals with Scheie syndrome have a deficiency of the enzyme alpha-L-iduronidase. Individuals with Scheie syndrome have normal intelligence, height, and life expectancy. Symptoms include stiff joints, carpal tunnel syndrome, backward flow of blood into the heart (aortic regurgitation), and clouding of the cornea that may result in the loss of visual acuity. The onset of symptoms in individuals with Scheie syndrome usually occurs around the age of five. (For more information on this disorder, choose "Scheie" as your search term in the Rare Disease Database.)
DiFerrante syndrome (mucopolysaccharidosis VIII) is a disorder described in a single patient with clinical and biochemical features of Morquio and Sanfilippo syndromes. The disorder had been reported to be due to a deficiency of glucosamine-6-sulfate sulfatase. Subsequently, this disorder was called MPS VIII (DiFerrante syndrome). Dr. DiFerrante later found that the enzyme was normal in his patient, and the disorder had been misdiagnosed. Therefore, Diferrante syndrome is not a valid medical disorder.
The mucolipidoses are a family of similar disorders, producing symptoms very much like those of the mucopolysaccharidoses (MPS).
I-cell disease, or mucolipidosis type II, resembles Hurler syndrome and the two disorders are very difficult to distinguish. I-cell disease has similar physical and mental deterioration as MPS I, but usually occurs earlier and is more severe. I-cell disease is characterized by diffused deficiency of lysosomal enzymes within the cell and is not associated with excretion of mucopolysaccharides in the urine.
Pseudo-Hurler polydystrophy (mucolipidosis type III) is a rare genetic metabolic disorder characterized by a defective enzyme known as UPD-N-acetylglucosamine-1-phosphotransferase. This defective enzyme ultimately results in the accumulation of certain complex carbohydrates (mucopolysaccharides) and fatty substances (mucolipids) in various tissues of the body. The symptoms of this disorder are similar to, but less severe than, those of I-cell disease (mucolipidosis type II) and may include progressive joint stiffness, curvature of the spine (scoliosis), and/or skeletal deformities of the hands (e.g., claw-hands). Growth delays accompanied by deterioration of the hip joints typically develop in children with pseudo-Hurler polydystrophy. Additional symptoms may include clouding of the corneas of the eyes, mild to moderate coarseness of facial features, mild mental retardation, easy fatigability, and/or heart disease. Pseudo-Hurler polydystrophy is inherited as an autosomal recessive trait. (For more information on this disorder, choose "pseudo-Hurler polydystrophy" as your search term in the Rare Disease Database.)
Mucolipidosis IV is a rare inherited metabolic disorder believed to be characterized by a deficiency of transport channel receptor protein, based upon the recent discovery of the mucolipidosis IV gene. This deficiency may lead to the accumulation of certain fatty substances (mucolipids) and certain complex carbohydrates (mucopolysaccharides) within the cells of many tissues of the body. Mucolipidosis IV is characterized by mental retardation; severe impairment in the acquisition of skills requiring the coordination of muscular and mental activities (psychomotor retardation); diminished muscle tone (hypotonia); clouding (opacity) of the clear portion of the eyes through which light passes (cornea); and/or degeneration of the nerve-rich membrane lining the eyes (retinal degeneration). Mucolipidosis IV is inherited as an autosomal recessive genetic trait.
(For more information about the mucolipidoses, choose "ML Disorder" as your search term in the Rare Disease database.)
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.
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
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
For information about clinical trials sponsored by private sources, contact:
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.
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MPS Society Brochure.
MPS Research Funding Center Bulletin.
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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.
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Berkow R., ed. The Merck Manual-Home Edition. Whitehouse Station, NJ: Merck Research Laboratories; 1997:1308.
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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.
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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.
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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.
Report last updated: 2008/04/05 00:00:00 GMT+0