Mucopolysaccharidoses (MPS disorders) are a group of rare genetic disorders caused by the deficiency of one of ten specific lysosomal enzymes, resulting in an inability to metabolize complex carbohydrates (mucopolysaccharides) into simpler molecules. The accumulation of these large, undegraded mucopolysaccharides in the cells of the body causes a number of physical symptoms and abnormalities.
Mucopolysaccharidosis type I (MPS I) is a form of MPS caused by a deficiency of the enzyme alpha-L-iduronidase. The most severe form of MPS I is often called Hurler syndrome (or MPS IH). It is named for the physician, Gertrud Hurler, who first described the disorder in 1919. A milder form of MPS I is called Scheie syndrome (or MPS IS), and the name Hurler-Scheie (MPS IH/S) is sometimes applied to an intermediate form that does not fit clearly in either the milder or more severe category.
Infants with MPS I usually appear normal at birth, but may have inguinal and umbilical hernias. The diagnosis of MPS I is commonly made between 6 and 24 months of age when the patient may exhibit coarse facial features, clouding of the cornea, enlarged liver and spleen, a large tongue, skeletal abnormalities, poor growth, joint stiffness, and a prominent forehead.
MPS IH or Hurler syndrome, the most severe form of MPS I, is characterized by high concentrations of mucopolysaccharides, dermatan and heparan sulfates in the urine. Symptoms first become evident at 6 months to 2 years of age with developmental delay, recurrent urine and upper respiratory infections, noisy breathing and a persistent nasal discharge. Hydrocephalus is commonly present after the age of 2-3 years. (For more information on this disorder, choose “hydrocephalus” as your search term in the Rare Disease Database.) Other physical manifestations of this disorder may include clouding of the cornea of the eye, unusually large tongue, misaligned teeth, the development of a curved back and severe joint stiffness with clawlike hands. Mental development of Hurler syndrome usually reaches a peak at about 2 years of age with progressive mental retardation thereafter.
In the milder form of MPS I, known as Scheie syndrome, patients typically have normal intelligence, stature and life expectancy, but suffer from physical symptoms such as stiff joints, clouding of the cornea, and flow of blood from the aorta back into the left ventricle of the heart (aortic regurgitation). The onset of symptoms in patients with Scheie syndrome usually occurs after the age of 5 years. However, diagnosis is commonly delayed to between 10 to 20 years of age.
Hurler-Scheie syndrome, the intermediate form, is characterized by normal intelligence but progressive physical involvement which is milder than the physical signs and symptoms associated with Hurler syndrome. Corneal clouding, joint stiffness, deafness and valvular heart disease can develop by the early to mid-teens, causing significant impairment.
Signs and symptoms of MPS I occur as a result of a deficiency of the enzyme, alpha-L-iduronidase deficiency, needed to break down or metabolize complex carbohydrates (mucopolysaccharides).
The disorder is transmitted genetically, with each parent contributing one recessive gene carrying exactly the same type of genetic inheritance. Human traits including the classic genetic diseases, are the product of the interaction of two genes for that condition, one received from the father and one from the mother.
In recessive disorders, the condition does not appear unless a person inherits the same defective gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease, but generally will not exhibit symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.
MPS I tends to affect males and females equally with an incidence of about 1 in 100,000 live births.
Prenatal diagnosis of MPS I is now possible through amniocentesis and sampling of a tissue layer in the embryo (chorionic villus sampling).
Laronidase (Aldurazyme), an enzyme replacement therapy, has been approved by the U.S. Food and Drug Administration (April 2003) for treating patients with the Hurler and Hurler-Scheie forms of MPS I and for patients with the Scheie form who exhibit moderate to severe symptoms. Aldurazyme is manufactured by BioMarin Pharmaceutical Inc. and the Genzyme Corporation. It is the first treatment approved specifically for Hurler syndrome. For information about Aldurazyme, contact:
BioMarin Pharmaceutical Inc.
105 Digital Drive
Novato, CA 94949
Telephone. (415) 506-6700
Fax. (415) 382-7889
Patient Information. (415) 506-6100
500 Kendall Street
Cambridge, MA 02142
Telephone. (617) 252-7500
Fax. (617) 252-7600
Other treatment is symptomatic and supportive. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, specialists who assess and treat disorders of the nervous system (neurologists), specialists who diagnose and treat skeletal abnormalities (orthopedists), specialists who diagnose and treat heart abnormalities (cardiologists), physical therapists, and/or additional health care professionals may need to systematically and comprehensively plan an affected child's treatment. Medical and genetic counseling services will be useful to affected individuals and family.
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 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
For information about clinical trials sponsored by private sources, contact:
Scientists are studying the replacement of defective enzymes via enzyme replacement therapies and/or bone marrow transplants. Scientific study of gene replacement in animal models raises the hope that gene replacement therapy may someday be made available to people with genetic disorders such as MPS.
Fairview University Medical Center in Minneapolis is sponsoring a phase II study of bone marrow or umbilical cord blood transplantation in patients with MPS I and other lysosomal storage (and related) disorders. This study is sponsored by Fairview University Medical Center. For information, contact the study chair, Charles Peters, at (612) 624-5407.
Physicians at the Cedars-Sinai Medical Center and the Children’s Hospital Los Angeles are investigating the use of in utero bone marrow transplantation (BMT) to treat specific genetic conditions. Cells isolated from the father’s bone marrow are transplanted during the first trimester of pregnancy (before 14 weeks of gestation) in fetuses with a confirmed diagnosis of Wiskott-Aldrich syndrome, chronic granulomatous disease, alpha thalassemia, MPS I, metachromatic leukodystrophy and Krabbe disease. The diagnosis must be confirmed before 11 weeks of gestation. Other MPS storage disorders are not eligible for this study currently. For more information, contact:
Dr. Rena Falk or Dr. William Wilcox
Division of Genetics
Ceders-Sinai Medical Center
444 S. San Vicente Blvd. Suite 1001
Los Angeles, CA 90048
Tel: (310) 855-6451
Fax: (310) 659-0491
Dr. Robert Parkman
Division of Transplant Immunology
Children’s Hospital Los Angeles
4650 Sunset Blvd.
Los Angeles, CA 90027
Following the FDA approval of laronidase (Aldurazyme) for treating patients with Hurler syndrome, the companies sponsoring this enzyme replacement therapy, BioMarin Pharmaceutical Inc. and the Genzyme Corporation, have agreed with the FDA on a number of post-marketing commitments, including obtaining long-term information related to the natural history of MPS and the safety and efficacy of Aldurazyme. For information on how to contact these companies, see the Standard Therapies section of this report.
Contact for additional information about mucopolysaccharidosis type I:
John Barranger, PhD, MD
Director, Lysosomal Storage Disease, Clinical Care Network
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