Hurler Syndrome
Hurler Syndrome, also known as Mucopolysaccharidosis Type I (MPS I), is an autosomal recessive lysosomal storage disorder caused by deficiency of the alpha-L-iduronidase enzyme.
PrintHurler Syndrome, also known as Mucopolysaccharidosis Type I (MPS I), is an autosomal recessive lysosomal storage disorder caused by deficiency of the alpha-L-iduronidase enzyme.
There are three clinical phenotypes. Hurler Syndrome is the result of two severe mutations and absent or negligible enzyme activity, while residual enzyme function results in attenuated phenotypes of Hurler-Scheie Syndrome and Scheie Syndrome.
Molecular analysis is the only test that can clearly indicate the diagnostic or carrier status, as well as differentiate between the three phenotypes. Biochemical testing does not always distinguish the enzymatic activity between carriers and affected patients, and between the clinical phenotypes, since these are caused by differences in the combination of mutant alleles, polymorphisms and environmental factors.
The Ambry Test: Hurler Syndrome is a full Gene Sequence Analysis of the IDUA gene that detects mutations in over 95% of affected patients.
MPSI is an autosomal recessive lysosomal storage disorder that is caused by mutations in the IDUA gene, which cause a deficiency of the enzyme alpha-L-iduronidase. The lack of enzyme results in accumulation of glycoaminoglycans (GAGs) in the lysosomes, leading to systemic accumulation of heparin and dermatan sulfate throughout the body. There are three clinical phenotypes: Hurler is the result of two severe mutations and 0-3% enzyme activity, while residual functionality from pseudo-deficiency results in attenuated Hurler-Scheie or Scheie syndromes. Symptoms include severe progressive mental retardation, skeletal deformities including coarsening of the facial features, hepatosplenomegaly and corneal clouding in the first year of life.1 Death can occur in the first decade of life from obstructive airway disease, respiratory infections or cardiac complications, with average survival of 11.6 years of age.2 The Hurler-Scheie phenotype includes most of the skeletal problems, but with later onset in the teens and with little mental retardation. Scheie patients have the mildest phenotype which may not be diagnosed until adulthood. Symptoms include aortic valve disease, stiff joints, corneal clouding, mild visceral organ problems, and little to no mental retardation.1,2 Prevalence of MPSI is about 1 in 100,000.2
Treatment can include enzyme replacement therapy, surgery to correct skeletal malformations, and prevention of secondary complications. Enzyme replacement therapy can reduce non-neurological symptoms and pain, while bone marrow transplantation (BMT) and umbilical cord blood transplantation (UCBT) can halt neurologic degeneration and improve abnormal physical characteristics, except for those affecting the skeleton and eyes. BMT and UCBT are high-risk procedures with high rates of morbidity and mortality.
Molecular analysis of the IDUA gene is the only test that can clearly indicate the diagnostic or carrier status, as well as differentiate between the three phenotypes. Biochemical testing does not always distinguish the enzymatic activity between carriers and affected patients, and between the clinical phenotypes, since these are caused by differences in the combination of mutant alleles, polymorphisms and environmental factors.
The Ambry Test: Hurler Syndrome is a full gene sequence analysis performed by PCR-based double-stranded automated sequencing in the sense and antisense directions for exons 1-14 of the IDUA gene, plus at least 20 bases into the 5’ and 3’ ends of all the introns. Specic mutation analysis for individual IDUA mutations known to be in the family is also available.
Gene sequence analysis of IDUA is expected to detect mutations in over 95% of affected patients1 (clinical sensitivity). The Hurler Syndrome test detects ~98% of those IDUA mutations described as causing the disease (analytic sensitivity).
Blood: Collect 3-5 cc from adult or 2 cc minimum from child into EDTA purple-top tube (rst choice) or ACD yellow-top tube (second choice). Store at room temperature or refrigerate. Ship at room temperature.
Saliva: Collect 2 ml into Oragene™ DNA Self-Collection container. Store and ship at room temperature.
DNA: Send 20 μg in TE at 50-100 ng/μl. Store frozen and ship on ice or dry ice.
Prenatal: Prenatal testing is available. Please call an Ambry Genetic Counselor to discuss your case.
| Test Code | Technique | CPT Codes |
|---|---|---|
| 2160 | IDUA Gene Sequence Analysis | 83891x1, 83894x12, 83898x11, 83904x22, 83909x22, 83912x1 |
| Technique | Days |
|---|---|
| IDUA Gene Sequence Analysis | 10-21 |
1 Beesley CE et al. Hum Genet. 2001:109;503-511.
2 Moore D et al. Orphanet J Rare Dis. 2008:16(3);24.
3 Wraith JE et al. Pediatrics. 2007;120:37-46.