Mucopolysaccharidosis I (MPS I) Disease (Hurler, Hurler-Scheie, Scheie Syndromes)
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Metabolic defect: alpha-L-iduronidase deficiency
Other glycosaminoglycans metabolism diseases (mucopolysaccharidoses): MPS II | MPS III | MPS IV | MPS VI | MPS VII
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| Etiology & Pathogenesis [1,2]Enzyme deficiency results in progressive accumulation of the glycosaminoglycans (gags) dermatan and heparan sulfate. Key Symptom Images
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| Hernia |
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Corneal clouding |
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Coarse facial features |
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Claw hand |
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Image Credits: Hernia courtesy Atlas of Metabolic Diseases, Arnold, 1998. Corneal clouding courtesy of Desnick et al., 2003, with permission from author and publisher. Coarse facial features courtesy of The National MPS Society, Inc. Clinical Description and Progression/Prognosis [1,3]Glycosaminoglycans (GAGs), which are important constituents of the extra cellular matrix, joint fluid, and connective tissue throughout the body, progressively accumulate in the lysosome. Ultimately the accumulation causes cell, tissue, and organ dysfunction by largely unknown pathophysiological mechanisms. Clinical manifestations of MPS I show a chronic and progressive course that is multisystemic in nature. The disease is highly heterogeneous, spanning a spectrum of severity. Individuals with the most severe form of MPS I typically suffer from a number of progressively debilitating symptoms, including mental retardation. Their life span is less than 10 years. Individuals at the less severe end of the disease spectrum can have some of the same physical symptoms, but they generally retain normal intellect and stature, and may have a normal life span. Hurler, Hurler-Scheie, and Scheie syndromes are historical terms used to describe the most severe, intermediate, and least severe forms of MPS I. However, because there is no clear delineation between these classifications, patients are best described as having severe or less severe MPS I disease. Inheritance pattern: autosomal recessive Incidence: pan-ethnic [1]; 1 in 100,000 live births Diagnosis: enzyme assay; prenatal diagnosis possible through amniocentesis Conditions with similar presentations: other lysosomal storage disorders, particularly other mucopolysaccharide diseases and multiple sulfatase deficiency. Management: enzyme replacement therapy; bone marrow transplantation in some cases Other medical care: symptom management
 Developmental delay and severe mental retardation usually evident by 18 months, patient generally does not progress in development but plateaus for a number of years followed by a slow decline in intellectual capabilities. Structural CNS manifestations hydrocephalus and an associated increase in intracranial pressure may lead to brain compression, spinal cord compression, which can result from thickening of the dura or subluxation of vertebrae. Peripheral nervous system poor hand function, in part as a result of carpal tunnel syndrome. Gastrointestinal Distended abdomen, typically caused by the progressive enlargement of the liver and/or spleen. Periodic loose stools and diarrhea, sometimes alternating with periods of severe constipation due to storage within ganglion cells of the enteric nervous system Hernias, both inguinal and umbilical, are common in patients with MPS I. Back to categories Skeletal and joint manifestations (including gibbus deformity of the back, or dorsolumbar kyphosis) in patients with less severe forms of MPS I In severe cases, skeletal involvement can be detected in the first year of life by radiological methods Kyphosis, scoliosis, and severe back pain are also common Progressive arthropathy affecting all joints, and eventually leading to the loss of (or severe restriction of) range of motion Growth retardation, typically involving the trunk more than the limbs. Back to categories Chronic rhinitis and rhinorrhea without obvious infections are common Storage within the oro-pharynx with associated enlargement of the tongue, tonsils, and adenoids can lead to significant upper airway complications Narrowed trachea, thickened vocal cords, and redundant tissue in the upper airway may contribute to airway obstruction and can result in sleep apnea Lung volumes are often reduced because of the small thorax and hepatosplenomegaly limiting excursion of the diaphragm Recurrent respiratory infections are common Respiratory insufficiency is a major cause of mortality Ocular Corneal clouding Cardiovascular Clinical complications related to heart disease occur particularly during the later stages of the disease. Storage of certain glycosaminoglycans within and around the valve leaflets results in their thickening and stiffening, which can lead to progressive mitral and aortic regurgitation or stenosis Mitral regurgitation is the most common valvular disease in severely affected MPS I patients Cerebral Hydrocephalus Back to categories
1. Neufeld EF, Muenzer J. The mucopolysaccharidoses. In: The Metabolic Bases of Inherited Disease. New York: mcgraw Hill, 2001; 3421-3452.
2. Clarke LA. Clinical diagnosis of lysosomal storage diseases. In: Applegarth DA, Dimmick JE, JG Hall. Organelle Diseases: Clinical Features, Diagnosis, Pathogenesis and Management. London: Chapman and Hall 1997; 37-71.
3. Cleary MA, Wraith JE. The presenting features of mucopolysaccharidosis type IH (Hurler syndrome). Acta Paediatr. 1995;84:337-339. |
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