Hurler Syndrome, Full Gene Analysis
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 / Alpha-L-Iduronidase, Blood or IDST / 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.
Identifying mutations within the IDUA gene
Confirmation of a diagnosis of mucopolysaccharidosis type I (MPS-I)
Carrier testing when there is a family history of MPS- I, but disease-causing mutations have not 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
A small percentage of individuals who are carriers or have a diagnosis of mucopolysaccharidosis type I (MPS-I) may have a mutation that is not identified by this method (eg, large genomic deletions, promoter mutations). The absence of a mutation, therefore, does not eliminate the possibility of positive carrier status or the diagnosis of MPS-I. The preferred approach to carrier testing is to first document the presence of an IDUA gene mutation in an affected family member.
In some cases, DNA alterations of undetermined significance may be identified.
Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.
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.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.
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