Mucopolysaccharidosis Type I via the IDUA Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
7713 IDUA 81406 81406,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7713IDUA81406 81406, 81479 $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

The mucopolysaccharidoses (MPS) are a group of inherited disorders caused by defects in lysosomal enzymes responsible for the stepwise degradation of glycosaminoglycans (GAGs). Each enzyme deficiency results in progressive storage of distinct GAGs in multiple organ systems and subsequent abnormalities. Although MPS share several symptoms, including physical and mental developmental abnormalities, they may differ even within the same enzyme deficiency. Seven clinically distinct types can be recognized (Types I, II, III, IV, VI, VII, and IX). Based on the biochemical and genetic defects, MPS III and IV are further divided in four and two subtypes, respectively. Deficiencies in eleven enzymes have been implicated in the various MPS (Neufeld and Muenzer 2001). See also the National MPS Society at (www.mpssociety.org).

MPS I is a multisystemic disorder caused by deficiency in lysosomal alpha-L-iduronidase and subsequent systemic accumulation of dermatan and heparan sulfates. Historically, three major clinical subtypes are recognized on the basis of the age of onset, severity and disease course (Neufeld and Muenzer 2001; Clarke and Heppner 2011; Coutinho et al. 2012).

1) Hurler syndrome is the most severe and frequent form of MPS I. It is characterized by onset in infancy and death by the first decade of life, as the result of heart or lung failure. Symptoms include coarse facial features, corneal clouding, hydrocephalus, heart disease, respiratory difficulties, hepatosplenomegaly, joint stiffness, learning disabilities, and mental retardation.

2) Hurler-Scheie syndrome is characterized by onset in childhood and intermediate severity, progressive somatic involvement with normal intelligence and survival to adulthood.

3) Scheie syndrome is the mildest and most heterogeneous form. Symptoms appear after the age of five years and include stiff joint and heart disease. Life span is usually normal (Thomas et al. 2010).

Due to the wide range of clinical manifestations and the lack of clear delineation between the three subtypes, patients are best described as having severe and attenuated forms of MPS I disease (Neufeld and Muenzer 2001).

MPS I affects people worldwide with an estimated prevalence of 1:100,000 per live births (www.orpha.net).

Genetics

MPS I is inherited in an autosomal recessive manner and results from pathogenic variants in the IDUA gene (Scott et al. 1992; Lee-Chen et al. 1999; Moskowitz et al. 1993). Over 200 causative variants have been reported in patients from various ethnic and geographical populations and include missense, nonsense, splicing, small insertions or deletions and indels. Large pathogenic deletions in the IDUA gene have not been reported (Human Mutation Gene Database).

There are no clear genotype-phenotype correlations because most pathogenic variants are private or occur with low frequencies. Nonetheless, patients with a nonsense mutation on both alleles typically develop a severe clinical phenotype (Terlato and Cox GF 2003). In addition, genetic and other modifying factors may contribute to the clinical phenotype (Clarke et al. 1994)

The IDUA gene encodes the lysosomal alpha-L-iduronidase enzyme, which hydrolyzes the terminal a-L-iduronic acid residues of dermatan sulfate and heparan sulfate.

Testing Strategy

This test provides full coverage of all coding exons of the IDUA gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Clinical Sensitivity - Sequencing with CNV PG-Select

Pathogenic variants in the IDUA gene were identified in about 97% of alleles in patients biochemically proven to have MPS I (Beesley et al. 2001).

Thus far, large pathogenic deletions in the IDUA gene have not been reported (Human Mutation Gene Database).

Indications for Test

Confirmation of the diagnosis of MPS I in patients with clinical features and radiological findings suggestive of MPS such as increased urinary dermatan and heparin sulfate excretion, and reduced alpha-L-iduronidase activity; and identification of asymptomatic heterozygous carriers.

Gene

Official Gene Symbol OMIM ID
IDUA 252800
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
Fetal Concerns Panel

Citations

  • Beesley CE, Meaney CA, Greenland G, Adams V, Vellodi A, Young EP, Winchester BG. 2001. Mutational analysis of 85 mucopolysaccharidosis type I families: frequency of known mutations, identification of 17 novel mutations and in vitro expression of missense mutations. Hum. Genet. 109: 503–511. PubMed ID: 11735025
  • Clarke LA, Heppner J. 2011. Mucopolysaccharidosis Type I. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301341
  • Clarke LA, Nelson PV, Warrington CL, Morris CP, Hopwood JJ, Scott HS. 1994. Mutation analysis of 19 North American mucopolysaccharidosis type I patients: identification of two additional frequent mutations. Human mutation 3: 275–282. PubMed ID: 8019563
  • Coutinho MF, Lacerda L, Alves S. 2012. Glycosaminoglycan Storage Disorders: A Review. Biochemistry Research International 2012: 1–16. PubMed ID: 22013531
  • Human Gene Mutation Database (Bio-base).
  • Lee-Chen GJ, Lin SP, Tang YF, Chin YW. 1999. Mucopolysaccharidosis type I: characterization of novel mutations affecting alpha-L-iduronidase activity. Clin. Genet. 56: 66–70. PubMed ID: 10466419
  • Moskowitz SM, Tieu PT, Neufeld EF. 1993. Mutation in Scheie syndrome (MPS IS): a G-->A transition creates new splice site in intron 5 of one IDUA allele. Hum. Mutat. 2: 141–144. PubMed ID: 8318992
  • Neufeld EF, Muenzer J. 2001. The Mucoploysaccharidoses. 136: 3421-3452.
  • Orphanet
  • Scott HS, Litjens T, Hopwood JJ, Morris CP. 1992. A common mutation for mucopolysaccharidosis type I associated with a severe Hurler syndrome phenotype. Hum. Mutat. 1: 103–108. PubMed ID: 1301196
  • Terlato NJ, Cox GF. 2003. Can mucopolysaccharidosis type I disease severity be predicted based on a patient’s genotype? A comprehensive review of the literature: Genetics in Medicine 5: 286–294. PubMed ID: 12865757
  • Thomas JA, Beck M, Clarke JTR, Cox GF. 2010. Childhood onset of Scheie syndrome, the attenuated form of mucopolysaccharidosis I. Journal of Inherited Metabolic Disease 33: 421–427. PubMed ID: 20532982

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

loading Loading... ×

ORDER OPTIONS

View Ordering Instructions

1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Total Price: $
×
Copy Text to Clipboard
×