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The mucopolysaccharidoses are a group of lysosomal storage disorders caused by the deficiency of any of the enzymes involved in the stepwise degradation of dermatan sulfate, heparan sulfate, keratan sulfate, or chondroitin sulfate (glycosaminoglycans; GAG). Accumulation of GAG (previously called mucopolysaccharides; MPS) in lysosomes interferes with normal functioning of cells, tissues, and organs. There are 11 known disorders that involve the accumulation of GAG. MPS disorders involve multiple organ systems characterized by coarse facial features, cardiac abnormalities, organomegaly, intellectual disabilities, short stature, and skeletal abnormalities.
Mucopolysaccharidosis I (MPS I) is an autosomal recessive disorder caused by a reduced or absent activity of the enzyme alpha-L-iduronidase due to mutations in the IDUA gene. More than 100 mutations have been reported in individuals with MPS I. Deficiency of alpha-L-iduronidase can result in a wide range of phenotypes categorized into 3 syndromes: Hurler syndrome (MPS IH), Scheie syndrome (MPS IS), and Hurler-Scheie syndrome (MPS IH/S). Because these syndromes cannot be distinguished biochemically, they are also referred to as MPS I and attenuated MPS I.
Clinical features and severity of symptoms of MPS I are variable, ranging from severe disease to an attenuated form that generally presents at a later onset with a milder clinical presentation. In general, symptoms may include coarse facies, progressive dysostosis multiplex, hepatosplenomegaly, corneal clouding, hearing loss, intellectual disabilities or learning difficulties, and cardiac valvular disease. The incidence of MPS I is approximately 1 in 100,000 live births. Treatment options include hematopoietic stem cell transplantation and enzyme replacement therapy.
A diagnostic workup in an individual with MPS I typically demonstrates elevated levels of urinary GAG (MPSQN / Mucopolysaccharides [MPS], Quantitative, Urine) and increased amounts of both dermatan and heparan sulfate detected on thin-layer chromatography (MPSSC / Mucopolysaccharides [MPS] Screen, Urine). Reduced or absent activity of alpha-L-iduronidase in blood spots, fibroblasts (IDST / Alpha-L-Iduronidase, Fibroblasts), leukocytes, or whole blood (IDSWB / Alpha-L-Iduronidase, Blood) can confirm a diagnosis of MPS I; however, enzymatic testing is not reliable for carrier detection. Molecular sequence analysis of the IDUA gene allows for detection of the disease-causing mutation in affected patients and subsequent carrier detection in relatives. To date, a clear genotype-phenotype correlation has not been established.
Diagnosis of mucopolysaccharidosis I (MPS I), Hurler syndrome (MPS IH), Scheie syndrome (MPS IS), and Hurler-Scheie syndrome (MPS IH/S) in fibroblasts
Mucopolysaccharidosis I is characterized by very low or absent activity of alpha-L-iduronidase; differentiation between Hurler syndrome (MPS IH), Scheie syndrome (MPS IS), and Hurler-Scheie syndrome (MPS IH/S) is based on clinical findings.
This test cannot reliably determine carrier status for mucopolysaccharidosis I (MPS I).
The presence of a pseudodeficiency allele may cause reduced activity of alpha-L-iduronidase with the use of artificial substrate, which is used in this assay. This can result in values below the normal reference range, but will typically be greater than levels found in patients with MPS I.
Interfering factors include lack of viable cells, bacterial contamination, failure to transport tissue in an appropriate media, excessive transport time, and exposure of the specimen to temperature extremes (freezing or >30 degrees C).
> or =0.87 nmol/min/mg protein
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