TEST CATALOG ORDERING & RESULTS SPECIMEN HANDLING CUSTOMER SERVICE EDUCATION & INSIGHTS
Test Catalog

Test ID: MPS1Z    
Hurler Syndrome, Full Gene Analysis, Varies

Useful For Suggests clinical disorders or settings where the test may be helpful

Identifying variants 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 variants have not been previously identified

Genetics Test Information Provides information that may help with selection of the correct genetic test or proper submission of the test request

Testing includes full gene sequencing of the IDUA gene.

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

If skin biopsy is received, fibroblast culture for genetic test will be performed at an additional charge.

 

The following algorithms are available in Special Instructions:

-Lysosomal Storage Disorders Diagnostic Algorithm, Part 1

-Newborn Screen Follow-up for Mucopolysaccharidosis Type I

 

For more information, see Newborn Screening Act Sheet Mucopolysaccharidosis Type I: Decreased Alpha-L-Iduronidase in Special Instructions.

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 variants 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 variants.

 

The recommended first-tier test for MPS-I is biochemical testing that measures alpha-L-iduronidase enzyme activity in blood: IDUAW / Alpha-L-Iduronidase, Leukocytes or PLSD / Lysosomal and Peroxisomal Storage Disorders Screen, Blood Spot. Individuals with decreased or absent enzyme activity are more likely to have 2 identifiable variants in the IDUA gene by molecular genetic testing. However, enzymatic testing is not reliable to detect carriers. Additionally, measurement of mucopolysaccharides in blood can aid in diagnosis and ongoing therapeutic monitoring (MPSBS / Mucopolysaccharidosis, Blood Spot).

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.

Interpretation Provides information to assist in interpretation of the test results

All detected alterations are evaluated according to American College of Medical Genetics and Genomics (ACMG) recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

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 variant that is not identified by this method (eg, large genomic deletions, promoter alterations). The absence of a variant, 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 variant 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.

  

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.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):405-424

2. 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

3. 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

4. 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

5. 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

Special Instructions Library of PDFs including pertinent information and forms related to the test