MUCOPOLYSACCHARIDOSIS TYPE IVA
GALNS Sequencing
DNA ANALYSIS
Also known as: MPS IVA; Morquio A disease

Description:

Mucopolysaccharidosis IVA is an autosomal recessive lysosomal storage disorder caused by a genetic deficiency of the N-acetylgalactosamine-6-sulfate sulfatase (GALNS). GALNS is required to degrade keratan sulfate (KS) and chondroitin-6-sulfate (C6S). The accumulation of undegraded substrates in lysosomes of the affected tissues leads to a systemic bone dysplasia. As in other mucopolysaccharidoses, MPS IVA patients show a broad spectrum of clinical severity. Phenotypes vary from the classical form with severe bone dysplasia (spondyloepiphyseal dysplasia), short trunk dwarfism, hearing loss, heart valve involvement, corneal opacity, and a life span of 20 to 30 years, to milder forms with fewer manifestations. The broad range of clinical phenotypes seen in MPS IVA is presumed to be the result of a wide variety of GALNS mutations. To date, over 90 different mutations have been identified including around 70 missense mutations. Sequence analysis of the entire GALNS gene is available on a clinical basis at the Medical Genetics Laboratories at Baylor College of Medicine .

Reasons for Referral:

  • Confirmation of a clinical diagnosis of Mucopolysaccharidosis IVA (Morquio A) disease.
  • Carrier testing for individuals with a positive family history for a GALNS mutation (molecular analysis of the affected relative is recommended).

Testing Methodology:

PCR amplification of the exons contained in the GALNS gene coding region will be performed on patient genomic DNA. Direct sequencing of amplification products is performed in both the forward and reverse directions using automated fluorescence dideoxy sequencing methods.

Specimen Requirements:

Blood: EDTA (purple-top) tubes: Adult: 14 cc; Child: 6 cc; Infant: 2-3 cc

Turnaround Time:

Index: 4 weeks

CPT Codes and Prices:

Index: 83891, 83898x14, 83894, 83904x28, 83909x28, 83912
Known Familial Mutation: 83891, 83898, 83894, 83904x2, 83909x2, 83912

Shipping Information

Forms:

>> Gene Sequencing Requisition

References:

Tomatsu, S.et al (2005). Mutation and Polymorphism Spectrum of the GALNS Gene in Mucopolysaccharidosis IVA (Morquio A). Human Mutation 26(6), 500-512.

Test Codes:

Index: 6400
Known Familial Mutation: 6405