• 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.

• 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.

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.

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