MPS I: Genetics

Heterozygous Carriers

  • Parents of affected children 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 (i.e., if one child has severe MPS I, other siblings will have the severe form and not the milder forms).
  • 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 is 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.

Genotype-Phenotype Correlations

  • Almost all individuals with MPS I have no detectable enzyme activity by enzyme assay; the amount 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.
  • Intermediate and attenuated MPS I are usually associated with 1 severe mutation and another mutation that permits production of some 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 (GeneTests).
  2. Analysis of α-L-iduronidase enzyme activity 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.

Mutation Analysis and Gene Therapy (University of Minnesota)
Gene therapy and mutation analysis including testing for newborns. Offers "The MPS Test," a patented test that allows a urine sample to be collected by non-medical persons, such as parents or patients, using a collection paper.

Genetics in Primary Care Institute (AAP)
The goal of this site is to increase collaboration in the care of children with known or suspected genetic disorders. Includes health supervision guidelines and other useful resources; a collaboration among the Health Resources & Services Administration, the Maternal and Child Health Bureau, and the American Academy of Pediatrics.


Pediatric Genetic Counseling

See all Pediatric Genetic Counseling services providers (5) in our database.

Pediatric Genetics

See all Pediatric Genetics services providers (5) in our database.

For other services related to this condition, browse our Services categories or search our database.


Author: Pilar L. Magoulas, MS, CGC - 2/2009
Reviewing Author: Pilar L. Magoulas, MS, CGC - 2/2016
Content Last Updated: 2/2016