Mucopolysaccharidosis Type I - Description

Other Names

Hurler syndrome
MPS I
Hurler-Scheie syndrome
Scheie syndrome

ICD-9

277.5, mucopolysaccharidosis (all types)

This is the ICD-9 code for the primary diagnosis. For additional detail and codes for related conditions, see MPS I ICD9 (PDF Document 55 KB)

Description

Mucopolysaccharidosis type I (MPS I) is an autosomal recessive lysosomal storage disorder resulting from deficiency of the enzyme α-L-iduronidase. Deficiency of this enzyme results in the accumulation of dermatan sulfate and heparan sulfate, which are complex sugars known as glycosaminoglycans (GAGs). The resulting accumulation of GAGs in the lysosomes leads to progressive, multi-system organ damage.

The clinical variability among the mucopolysaccharidoses is broad. Historically, individuals with the most severe form of MPS I were classified as having Hurler syndrome, whereas the intermediate form was called Hurler-Scheie syndrome, and the least severe form was designated Scheie syndrome. However, recent nomenclature prefers the terms "severe" MPS I for those previously considered to have Hurler syndrome and "attenuated" MPS I in those previously considered to have Hurler-Scheie or Scheie syndromes.

Some of the manifestations observed in affected individuals include:
  • hernias, inguinal and umbilical
  • facial features that become coarse over time
  • frequent upper airway infections with otitis media
  • hepatosplenomegaly
  • corneal clouding
  • cardiac involvement, valve disease
  • progressive skeletal dysplasia (dysostosis multiplex)
  • growth delay
  • profound neurological involvement (in the severe form only)
  • macrocephaly

Genetics

MPS I is an autosomal recessive condition caused by mutations in the IDUA gene. This gene encodes the protein α-L-iduronidase. Mutation analysis is clinically available and will detect mutations in 95% of individuals with MPS I. A genotype-phenotype correlation may identify those at risk for the more severe clinical manifestations. Parents of children with MPS I are obligate carriers of the condition and have a 25% chance of having other children with MPS I. Carriers do not have any known symptoms of MPS I. (For definitions of the genetic terms used here, see GeneTests.org Glossary).

Prognosis

The onset of symptoms and course of disease varies in MPS I, depending on the severity of the condition. If untreated, the prognosis of individuals with the severe form of MPS I is very poor, with onset very early in life and rapidly progressive manifestations, often resulting in death by ten years of age. Onset of symptoms in attenuated MPS I is usually in childhood or adolescence and survival to adulthood is common. Individuals with an attenuated form still require stringent clinical management, particularly related to their cardiac and skeletal manifestations.

Prevalence

MPS I is a rare condition that is seen in all populations. There are no known ethnic predilections; however, some mutations are more common in certain populations. The incidence of severe MPS I is estimated to be approximately 1 in 100,000, and the attenuated MPS I is even more rare. [Meikle: 1999] This could be a true reflection of the actual incidence or an underestimate due to ascertainment bias, with older, more mildly affected individuals being undiagnosed.

Impact

All individuals with MPS I require an extensive multi-disciplinary team approach to care given the significant multi-organ system involvement associated with this condition. Treatment and therapy costs can be staggering, yet are recommended life-long to decrease the morbidity and mortality of the condition while promoting optimal quality of life for individuals with and affected by MPS I. Any surgical procedure or illness can be protracted in affected individuals, which extends need for medical and rehabilitative services.

Helpful Articles

PubMed search for mucopolysaccharidosis type I in children, last 4 years.

Muenzer J.
The mucopolysaccharidoses: a heterogeneous group of disorders with variable pediatric presentations.
J Pediatr. 2004;144(5 Suppl):S27-34. PubMed abstract

Staba SL, Escolar ML, Poe M, Kim Y, Martin PL, Szabolcs P, Allison-Thacker J, Wood S, Wenger DA, Rubinstein P, Hopwood JJ, Krivit W, Kurtzberg J.
Cord-blood transplants from unrelated donors in patients with Hurler's syndrome.
N Engl J Med. 2004;350(19):1960-9. PubMed abstract
Review of bone marrow transplant as a treatment option in individuals with Hurler syndrome.

Wraith EJ, Hopwood JJ, Fuller M, Meikle PJ, Brooks DA.
Laronidase treatment of mucopolysaccharidosis I.
BioDrugs. 2005;19(1):1-7. PubMed abstract
Review of enzyme replacement therapy as a treatment option in MPS I.

Scriver CR, Beaudet AL, Sly WS, Valle D, Childs B, Kinzler KW, Vogelstein B ed.
The mucopolysaccharidoses. In The Metabolic and Molecular Basis of Inherited Disease.
8th ed ed. New York: McGraw-Hill, Medical Publishing Division; 2001. 0071163360 http://books.mcgraw-hill.com/getommbid.php?isbn=0071459960&template=om...

Mucopolysaccharidosis Type I Module Authors

Author: Pilar L. Magoulas, MS, CGC - 9/2011
Reviewing Author: David Viskochil, MD, PhD - 10/2011
Content Last Updated: 11/2011

The authors listed above are responsible for the overall Mucopolysaccharidosis Type I Module. Authors contributing to individual pages in the module are listed on those pages.

Page Bibliography

Meikle PJ, Hopwood JJ, Clague AE, Carey WF.
Prevalence of lysosomal storage disorders.
JAMA. 1999;281(3):249-54. PubMed abstract