Mucopolysaccharidosis Type I (MPS 1) Genetics

  • Parents of children affected by mucopolysaccharidosis (MPS I) are obligate heterozygous carriers.
  • Heterozygous carriers are asymptomatic.
  • If parents have a child with MPS I, they have a 25% chance of having another child with MPS I.
  • Unaffected siblings of a child with MPS I have a 2/3 chance of being a carrier.
  • Siblings of obligate carriers (i.e., aunts and uncles of the affected child) have a 50% chance of being a carrier.
  • Affected siblings typically present with similar features, and there is usually little intra-familial variability. If 1 child has severe MPS I, other affected siblings will have the severe form and not the milder forms. Likewise, if 1 child has an attenuated form, other affected siblings will have the attenuated form and not the severe form.
  • Carrier testing of at-risk family members via measurement of α-L-iduronidase enzyme activity in leukocytes is not a reliable method of carrier determination because of potential overlap in enzyme levels between carriers and unaffected individuals.
  • Carrier testing by molecular genetic testing of the IDUA gene is clinically available and most useful when both mutations in the affected individual are known. Targeted mutation analysis can then be conducted in other family members. Molecular genetic testing is also available on a clinical basis for carrier testing in the unrelated partners of individuals known to be a carrier.
  • In heterozygous carrier parents when the IDUA mutations are known, preimplantation genetic diagnosis with in vitro fertilization in fertility clinics can be successfully performed.

Genotype-Phenotype Correlations

  • Almost all individuals with MPS I have no detectable enzyme activity by enzyme assay. The level of α-Liduronidase enzyme activity does not correlate with disease severity.
  • Currently, more than 89 IDUA mutations have been identified. In general, any combination of 2 severe mutations, the most common being W402X and Q70X, leads to severe MPS I.
  • Attenuated MPS I is usually associated with 1 severe mutation and another mutation that permits production of some, albeit unmeasurable, residual enzyme activity.

Obtaining Tests

Prenatal testing and diagnosis are available for pregnancies at increased risk for MPS I.

  1. Contact the selected lab prior to obtaining the sample. See Testing Laboratories for MPS I (Genetic Testing Registry).
  2. Analysis of α-L-iduronidase enzyme activity is measured in cultured cells obtained by amniocentesis at 16-18 weeks of gestation or chorionic villus sampling (CVS) at about 10-12 weeks of gestation. Caution: This test is not 100% sensitive and may produce false negative results (e.g., fetus is reported to be unaffected, but is affected). See Mucopolysaccharidosis Type I (GeneReviews) for more details.
  3. If both mutations are known, molecular genetic testing of the at-risk fetus can be performed by mutation analysis from DNA extracted from cells obtained by CVS or amniocentesis. This is the preferred method.

Follow-Up with Genetics or MPS Center

Annual follow-up is recommended to assess appropriate interventions, evaluate new findings and available interventions, and coordinate care.


Information & Support

For Professionals

Lysosomal Diseases Testing (Thomas Jefferson University)
Provides instructions on shipping and sample requirements for patient and carrier testing (does not include prenatal testing) to Thomas Jefferson University in Philadelphia, PA. Rarely do they provide mutation analysis on diagnosed patients. Site includes concise answers to frequently asked questions.

Baylor Miraca Genetics Laboratories (Baylor College)
Describes specimen requirements; turn-around-time is 2-10 days. Includes CPT codes and prices. Search MPS, Hurlers, or Mucopolysaccharidosis.

ARUP Laboratories
Provides quantitation of non-reducing ends of GAGs for management-related urine and plasma GAG analyses.

Greenwood Biochemical Genetics Laboratory
Provides enzyme detection of all MPS disorders with follow-up molecular genotype analyses on the initial sample.

Services for Patients & Families in Rhode Island (RI)

For services not listed above, browse our Services categories or search our database.

* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.

Authors & Reviewers

Initial publication: February 2009; last update/revision: May 2019
Current Authors and Reviewers:
Author: David Viskochil, MD, PhD
Authoring history
2016: update: Pilar L. Magoulas, MS, CGCR
2009: first version: Pilar L. Magoulas, MS, CGCA
AAuthor; CAContributing Author; SASenior Author; RReviewer