Iduronate Sulfatase, Fibroblasts
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Mucopolysaccharidosis II, (MPS II, Hunter syndrome) is an X-linked lysosomal storage disorder caused by the enzyme deficiency of iduronate sulfatase (IDS). The mucopolysaccharidoses are a group of disorders caused by the deficiency of any of the enzymes involved in the stepwise degradation of glycosaminoglycans (GAG). Accumulation of GAG (previously called mucopolysaccharides) in lysosomes interferes with normal functioning of cells, tissues, and organs.
Clinical features and severity of symptoms of MPS II are widely variable ranging from severe disease to an attenuated form, which generally presents at a later onset with a milder clinical presentation. In general, symptoms may include coarse facies, short stature, enlarged liver and spleen, hoarse voice, stiff joints, cardiac disease, and profound neurologic involvement leading to developmental delays and regression. Unlike MPS I (Hurler syndrome), corneal clouding is not typically present. Because MPS II is an X-linked disorder, it occurs almost exclusively in males with an estimated incidence of 1 in 100,000 male births (though symptomatic carrier females have been reported). Treatment options include hematopoietic stem cell transplantation and/or enzyme replacement therapy.
A diagnostic workup in an individual with MPS II typically demonstrates elevated levels of urinary GAG and increased amounts of both dermatan and heparan sulfate detected on thin-layer chromatography. Reduced or absent activity of IDS is diagnostic of MPS II; however, enzymatic testing is not reliable to detect carriers. Molecular sequence analysis of the IDS gene allows for detection of the disease-causing mutation in affected patients and subsequent carrier detection in female relatives. Currently, no clear genotype-phenotype correlations have been established.
Diagnosis of mucopolysaccharidosis II (MPS II, Hunter syndrome)
Values near zero suggest mucopolysaccharidosis II.
Values above the reference range are not clinically significant.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test cannot reliably determine carrier status for mucopolysaccharidosis II (MPS II).
Documentation of normal enzymatic activity of at least 1 other sulfatase is critical, as low levels of iduronate sulfatase enzyme activity are seen in the disorder multiple sulfatase deficiency, which has a similar clinical presentation to MPS II.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Martin R, Beck M, Eng C, et al: Recognition and diagnosis of mucopolysaccharidosis II (Hunter syndrome). Pediatrics 2008;121(2):e377-86
2. Wraith JE, Scarpa M, Beck M, et al: Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy. Eur J Pediatr 2008;167(3):266-277
3. Wasteson A, Neufeld EF: Iduronate sulfatase from human plasma. Meth Enzymol 1982;83:573-578
4. Enns GM, Steiner RD, Cowan TM: Lysosomal Disorders. In Pediatric Endocrinology and Inborn Errors of Metabolism. Edited by K Sarafoglou, GF Hoffmann, KS Roth, New York, McGraw-Hill Medical Division, 2009, pp 732