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Rheumatology 2011;50:v4–v12 doi:10.1093/rheumatology/ker394

Overview of the mucopolysaccharidoses
Joseph Muenzer1
The mucopolysaccharidoses (MPSs) are a group of rare, inherited lysosomal storage disorders that are clinically characterized by abnormalities in multiple organ systems and reduced life expectancy. The MPSs are heterogeneous, progressive disorders.Patients typically appear normal at birth, but during early childhood they experience the onset of clinical disease, including skeletal, joint, airway and cardiac involvement, hearing and vision impairment, and mental retardation in the severe forms of MPS I, MPS II and MPS VII and all subtypes of MPS III. There are two treatment options for patients with MPS that are directed at the underlyingpathophysiology: haematopoietic stem cell transplantation, which is useful for selected patients, and recombinant i.v. enzyme replacement therapy, which is available for MPS I, II and VI. Early diagnosis and treatment can improve patient outcomes and may reduce the disease burden on patients and caregivers. As skeletal and joint abnormalities are characteristic of many patients with MPS, rheumatologistsare positioned to recognize the features of the disease and to facilitate early diagnosis and referral. In this overview, the clinical features of the MPS disorders and a brief review of treatment options will be presented in order to aid the rheumatologist in recognizing the features of these rare genetic disorders.
Key words: Mucopolysaccharidoses, Genetic disorder, Glycosaminoglycan, Enzymereplacement therapy, Haematopoietic stem cell transplantation.

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The mucopolysaccharidoses (MPSs) are a group of rare genetic disorders of glycosaminoglycan (GAG) catabolism [1] (Table 1). Each MPS disorder is caused by a deficiency in the activity of a single, specific lysosomal enzyme required forGAG degradation. These diseases are biochemically characterized by an accumulation of partially degraded GAG within lysosomes and the elevation of GAG fragments in urine, blood [2, 3] and cerebral spinal fluid [4, 5]. The GAG accumulation results in progressive cellular damage, which can affect multiple organ systems and lead to organ failure, cognitive impairment and reduced life expectancy. Ofinterest to the rheumatologist, skeletal and joint abnormalities are a prominent feature of many of the MPS disorders; patients often present with skeletal dysplasia, decreased joint mobility, short stature and CTS [1]. With the exception of MPS II, the MPS disorders are inherited in an autosomal recessive pattern and affect both
1 Division of Genetics and Metabolism, Department of Pediatrics,University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Submitted 1 July 2011; revised version accepted 6 October 2011. Correspondence to: Joseph Muenzer, Division of Genetics and Metabolism, Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. E-mail:

males and females equally. MPS II is an X-linked recessive disorderthat generally affects only males, although rare female patients with MPS II have been described [6–8]. This can be caused by an X-autosome translocation and non-random X-chromosome inactivation in a carrier female. Early diagnosis and treatment can improve outcomes in MPS [9, 11], particularly in those disorders that can be treated with haematopoietic stem cell transplantation (HSCT) and thosefor which enzyme replacement therapy (ERT) is available (MPS I, II and VI). Yet, because the MPS disorders produce a wide variety of clinical presentations, diagnosis is often delayed, particularly in those patients without cognitive impairment [12]. Even those with severe cognitive and somatic disease may not be diagnosed until 12–18 months after the onset of symptoms, during which time...
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