Hurler Syndrome, Known Mutation
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Mucopolysaccharidosis type I (MPS-I) can be categorized into 3 syndromes, Hurler syndrome, Scheie syndrome, and Hurler-Scheie syndrome. MPS-I, inherited in an autosomal recessive manner, is caused by mutations in the IDUA gene. Furthermore, MPS-I is characterized by reduced or absent activity of the alpha-L-iduronidase enzyme.
Hurler syndrome (severe MPS-I) has early onset and consists of skeletal deformities, coarse facial features, corneal clouding, hepatosplenomegaly, cardiac involvement, hearing loss, and respiratory tract infections. Developmental delay is noticed as early as 12 months with death occurring usually before 10 years of age.
Hurler-Scheie syndrome and Scheie syndrome (attenuated MPS-I) have onset between 3 to 10 years of age and consist of corneal clouding, cardiac involvement, moderate to severe hearing loss, and progressive pulmonary disease. Typically skeletal and joint involvement is the most significant source of discomfort for attenuated MPS-I. Intellect with attenuated MPS-I is typically normal or nearly normal.
The IDUA gene is located on chromosome 4 and has 14 exons. IDUA is the only known gene to be associated with MPS-I, and the 3 syndromes appear to be caused by different combinations of mutations.
The recommended first-tier test for MPS-I is biochemical testing that measures alpha-L-iduronidase enzyme activity in blood or fibroblasts: IDSWB/60618 Alpha-L-Iduronidase, Blood or IDST/8780 Alpha-L-Iduronidase, Fibroblasts. Individuals with decreased or absent enzyme activity are more likely to have 2 identifiable mutations in the IDUA gene by molecular genetic testing. However, enzymatic testing is not reliable to detect carriers.
Carrier testing of individuals with a family history of mucopolysaccharidosis type I (MPS-I)
Diagnostic confirmation of MPS-I when familial mutations have been previously identified
An interpretive report based on the results, clinical presentation, and family history will be provided.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
The identification of a disease-causing mutation in an affected family member is necessary before predictive testing for other family members can be offered. If a familial mutation has not been previously identified, order HURLS/61481 Hurler Syndrome, Full Gene Analysis.
Analysis is performed only for the provided familial mutations. This assay does not rule out the presence of other mutations within this gene or within other genes that may be associated with metabolic disease.
We strongly recommend that patients undergoing predictive testing receive genetic counseling both prior to testing and after results are available.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Any error in the diagnosis or in the pedigree provided to us, including false-paternity, could lead to erroneous interpretation of results.
A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Muenzer J, Wraith JE, Clarke LA: International Consensus Panel on Management and Treatment of Mucopolysaccharidosis I. Mucopolysaccharidosis I: management and treatment guidelines. Pediatrics 2009;123(1):19-29
2. Scott HS, Bunge S, Gal A, et al: Molecular genetics of mucopolysaccharidosis type I: diagnostic, clinical, and biological implications. Hum Mutat 1995;6:288-302
3. Terlato NJ, Cox GF: Can mucopolysaccharidosis type I disease severity be predicted based on a patient's genotype? A comprehensive review of the literature. Genet Med 2003;5(4):286-294
4. Vijay S, Wraith JE: Clinical presentation and follow-up of patients with the attenuated phenotype of mucopolysaccharidosis type I. Acta Paediatr 2005;94(7):872-877