Diagnosis of mucopolysaccharidosis I (MPS I), Hurler syndrome (MPS IH), Scheie syndrome (MPS IS), and Hurler-Scheie syndrome (MPS IH/S)
Genetics Test Information Provides information that may help with selection of the correct test or proper submission of the test request
Diagnostic testing. Not recommended for carrier detection.
Fibroblasts are the preferred specimen since testing for other mucopolysaccharide storage diseases may be necessary.
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
The mucopolysaccharidoses are a group of lysosomal storage 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.
Mucopolysaccharidosis I (MPS I) is an autosomal recessive disorder caused by a reduced or absent activity of the alpha-L-iduronidase enzyme. Deficiency of the alpha-L-iduronidase enzyme can result in a wide range of phenotypes further categorized into 3 syndromes: MPS IH (Hurler syndrome), MPS IS (Scheie syndrome), and MPS IH/S (Hurler-Scheie syndrome).
Clinical features and severity of symptoms of MPS I are widely variable, ranging from severe disease to an attenuated form that generally presents at a later onset with a milder clinical presentation. Symptoms typically include coarse facies, progressive dysostosis multiplex, hepatosplenomegaly, corneal clouding, hearing loss, mental retardation 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 and increased amounts of both dermatan and heparan sulfate detected by thin-layer chromatography or liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis (MPSSC / Mucopolysaccharides Screen, Urine). Reduced or absent activity of alpha L-iduronidase is diagnostic of MPS I; however, enzymatic testing is not reliable to detect carriers. Molecular sequence analysis of IDUA (MPS1Z / Hurler Syndrome, Full Gene Analysis) allows for detection of the disease-causing mutation in affected patients and subsequent carrier detection in relatives. Currently, no clear genotype-phenotype correlations have been established.
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.
> or =0.87 nmol/min/mg protein
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.
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 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).
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Martins AM, Dualibi AP, Norato D, et al: Guidelines for the management of mucopolysaccharidosis type I. J Pediatr 2009 Oct:155(4 Suppl):S32-S46
2. Neufeld EF, Muenzer J: The Mucopolysaccharidoses. In: The Online Metabolic and Molecular Bases of Inherited Disease. Edited by D Valle, AL Beaudet, B Vogelstein B, et al: New York, NY: McGraw-Hill; 2014 Available at http://ommbid.mhmedical.com/content.aspx?bookid=971&Sectionid=62642135. Accessed May 04, 2015