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Test ID: MPS1Z Hurler Syndrome, Full Gene Analysis

Useful For

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

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
CULFB Fibroblast Culture for Genetic Test Yes No

Testing Algorithm

If skin biopsy is received, fibroblast culture for genetic test will be added and charged separately.

 

See Newborn Screen Follow-up for Mucopolysaccharidosis Type I in Special Instructions.

Method Name

Polymerase Chain Reaction (PCR) Followed by DNA Sequence Analysis

Reporting Name

Hurler Syndrome, Full Gene Analysis

Specimen Type

Varies


Specimen Required


Specimen preferred to arrive within 96 hours of collection.

 

Submit only 1 of the following specimens:

 

Preferred:

Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.

Specimen Stability Information: Ambient (preferred)/Refrigerated

 

Specimen Type: Cultured fibroblasts

Container/Tube: T-75 or T-25 flask

Specimen Volume: 1 Full T-75 flask or 2 full T-25 flasks

Specimen Stability Information: Ambient (preferred)/Refrigerated <24 hours

 

Specimen Type: Skin biopsy

Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin. Tubes can be supplied upon request (Eagle's minimum essential medium with 1% penicillin and streptomycin [T115]).

Specimen Volume: 4-mm punch

Specimen Stability Information: Refrigerated (preferred)/Ambient

 

Acceptable:

Specimen Type: Blood spot

Container/Tube: Whatman Protein Saver 903 Paper

Specimen Volume: 5 blood spots

Collection Instructions:

1. Let blood dry on the filter paper at ambient temperature in a horizontal position for 3 hours.

2. Do not expose specimen to heat or direct sunlight.

3. Do not stack wet specimens.

4. Keep specimen dry.

Specimen Stability Information: Ambient (preferred)/Refrigerated


Specimen Minimum Volume

Blood: 1 mL/Blood Spots: 5, 3-mm diameter

Specimen Stability Information

Specimen Type Temperature Time
Varies Varies

Clinical Information

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.

Reference Values

An interpretive report will be provided.

Interpretation

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

Clinical Reference

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

Day(s) and Time(s) Performed

Performed weekly, varies

Analytic Time

14 days

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

81406 IDUA (iduronidase, alpha-L-) (eg, mucopolysaccharidosis type I), full gene sequence

 

Fibroblast Culture for Genetic Test

88233-Tissue culture, skin or solid tissue biopsy (if appropriate)

88240-Cryopreservation (if appropriate)

 

LOINC Code Information

Test ID Test Order Name Order LOINC Value
MPS1Z Hurler Syndrome, Full Gene Analysis In Process

 

Result ID Test Result Name Result LOINC Value
53950 Result Summary 50397-9
53951 Result In Process
53952 Interpretation In Process
53953 Additional Information 48767-8
53954 Specimen In Process
53955 Source 31208-2
53956 Released By No LOINC Needed

Forms

1. Molecular Genetics: Biochemical Disorders Patient Information (T527) in Special Instructions

2. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (T576) is available in Special Instructions.

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

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