Mucopolysaccharidosis I
(MPS I)

About Mucopolysaccharidosis I (MPS I)

The mucopolysaccharidoses (MPS) are a group of inherited multisystem progressive disorders caused by deficiencies of the lysosomal enzymes that degrade complex disaccharides. The progressive accumulation of some of these molecules, called glycosaminoglycans (chondroitin sulfate, heparan sulfate, dermatan sulfate and keratan sulfate) in various tissues leads to the different phenotypes seen in the MPS disorders.

Mucopolysaccharidosis Ι (MPS Ι) is caused by a deficiency of the lysosomal enzyme α-L-iduronidase, leading to a buildup of its major substrates, the glycosaminoglycans (GAGs) dermatan sulfate and heparan sulfate, resulting in developmental delay and regression, plus respiratory, cardiac, and musculoskeletal dysfunction.1 MPS I is caused by mutations in the IDUA gene responsible for producing α-L-iduronidase.2 Symptoms of MPS I range over a continuum of severity but are generally divided into severe MPS I (historically called Hurler syndrome) and attenuated MPS I (historically called Hurler-Scheie and Scheie syndromes), with a variable age of onset, progression, and organ involvement.1 MPS I is inherited in an autosomal recessive manner.

There is considerable phenotypic overlap among several MPS disorders and the following symptoms may prompt further examination: Children may have coarse facial features, early frequent upper-respiratory infections (including otitis media), inguinal or umbilical hernia, developmental delay and regression. Both children and adults can have hepatosplenomegaly, joint stiffness, limited range of motion, joint contractures, carpal tunnel and corneal clouding.

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Mucopolysaccharidosis I<br>(MPS I)

Incidence

Together the incidence of the MPS disorders is estimated at 1/25,000 births. Severe MPS I occurs in approximately 1 in 100,000 newborns; the incidence of the attenuated form is estimated at 1 in 500,000 newborns.2-4

Program eligibility

The Roadmap2Rare Diagnostic Program* consists of an α-L-iduronidase enzyme assay with reflex to IDUA sequencing if deficient, and is for individuals suspected of having MPS I via:

  • Symptoms consistent with MPS I
  • Presumptive positive newborn screen for MPS I

*This testing program is not appropriate for carrier testing. 

About the test

Testing algorithm:

Patients suspected of having MPS I:

  • α-L-iduronidase will be assayed and if deficient will reflex to:
  • IDUA sequencing analysis (with copy number variant analysis if needed)
  • If either enzyme assay or IDUA sequencing has already been performed, these tests can be ordered individually

References

1. Arn P, Wraith J, Underhill L. Characterization of surgical procedures in patients with mucopolysaccharidosis type I: findings from the MPS I Registry. J Pediatr 2009; 154:859-64 e3.

2. Clarke LA. Mucopolysaccharidosis type 1. NCBI Bookshelf, a service of the National Library of Medicine, National Institutes of Health (NIH). Available at: ncbi.nlm.nih.gov/books/NBK1162/. Accessed July 20, 2018.

3. Beck M, Arn P, Giugliani R, et al. The natural history of MPS I: global perspectives from the MPS I Registry. Genet in Med. 2014;16(10):759.

4. Tomatsu S et al Newborn screening and diagnosis of mucopolysaccharidoses Mol Genet Metab. 2013 Sep-Oct; 110(0): 42–53.

This testing service has not been cleared or approved by the U.S. Food and Drug Administration. Testing services may not be licensed in accordance with the laws in all countries. The availability of specific test offerings is dependent upon laboratory location. The content on this page is provided for informational purposes only, not as medical advice. It is not intended to substitute the consultation, diagnosis, and/or treatment provided by a qualified licensed physician or other medical professionals.