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Diagnosis of mucopolysaccharidosis II (MPS II, Hunter syndrome) using dried blood spot specimens
The mucopolysaccharidoses are a group of 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: GAGs). Accumulation of GAGs (previously called mucopolysaccharides) in the lysosomes interferes with normal functioning of cells, tissues, and organs. Mucopolysaccharidosis II, (MPS II, Hunter syndrome) is an X-linked lysosomal storage disorder caused by the deficiency of iduronate sulfatase (IDS) enzyme and gives rise to the physical manifestations of the disease.
Clinical features and severity of symptoms are widely variable ranging from severe disease to an attenuated form, which generally has 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. As an X-linked disorder, Hunter disease occurs almost exclusively in males with an estimated incidence of 1 in 120,000 male births, although 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 glycosaminoglycans and increased amounts of both dermatan and heparan sulfate. Reduced or absent activity of IDS can confirm a diagnosis of MPS II; however, enzymatic testing is not reliable to detect carriers. Molecular genetic testing 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.
> or =1.5 nmol/h/mL
Specimens with results <1.5 nmol/h/mL in properly submitted specimens are consistent with iduronate-2-sulfatase deficiency (mucopolysaccharidosis II: MPS II). If clinically indicated, consider further confirmation by molecular genetic analysis of the IDS gene. Please note that this enzyme’s activity can also be reduced in multiple sulfatase deficiency (MSD; OMIM #272200). If clinically indicated, consider biochemical genetic testing of other sulfatases or molecular genetic testing of the SUMF1 gene to exclude MSD.
Normal results (> or =1.5 nmol/h/mL) are not consistent with iduronate-2-sulfatase deficiency.
This test cannot reliably determine carrier status for mucopolysaccharidosis II.