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Mucopolysaccharidosis Type IVA / Morquio Type A Disease via the GALNS Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
8305 GALNS 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8305GALNS81479 81479,81479 $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

18 days on average for standard orders or 13 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

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

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Jana Paderova, PhD

Clinical Features and Genetics

Clinical Features

The mucopolysaccharidoses (MPS) are a group of inherited disorders caused by defects in lysosomal enzymes responsible for the 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 (MPSIII-A to MPSIII-D; MPS IV-A and MPSIV-B).

To date, defects in eleven different enzymes have been associated with the various MPS. MPSIVA, also known as Morquio A disease, is caused by deficiency in N-acetylgalactosamine-6-sulfatase, while MPSIVB (Morquio B disease) is caused by deficiency in beta-galactosidase. Both enzymes are required for the degradation of the glycosaminoglycan keratan sulfate. Deficiency of either enzyme results in the abnormal accumulation of keratan sulfate mainly in the corneas and cartilage (Neufeld and Muenzer 2001).

The clinical manifestations of MPS IVA and B are identical. They are distinguished from other MPS by normal intelligence and skeletal dysplasia that results in short stature and skeletal abnormalities with secondary effects on the central nervous system. Various parts of the body may be affected including the wrists, knees, hips, ribs, chest and spine. Odontoid hypoplasia is a characteristic feature. Additional features include osteoporosis; coarse traits; corneal clouding leading eventually to loss of vision; widely spaced teeth with multiple cavities; repeated upper respiratory and ear infections that result in apnea and hearing loss; hernia; and hepatomegaly (Hughes et al. 1997; O’Brien et al. 1976).

In the classical and most severe form, symptoms begin during early childhood. If not treated, death occurs by the third decade of life, usually from complications as the result of spinal cord compression and airway obstruction. A milder form of MPS IV is characterized by a later age of onset; slow progression; mild bone and somatic involvement; and survival into late adulthood (Montaño et al. 2007; Solanki et al. 2013; Nelson et al. 1988).

MPSIV affects people worldwide with various incidences, ranging from 1:76,000 in Northern Ireland to 1:640,000 in Western Australia (Tomatsu et al. 2005). An incidence of 0.38:100,000 was reported in Germany (Baehner et al. 2005).

Genetics

MPS IVA is an autosomal recessive disease that results from defects in the GALNS gene (Fukuda et al. 1992). Over 200 pathogenic variants have been reported in patients from various ethnic populations. All types of variants have been reported. However, the vast majority were missense and nonsense mutations. Of note, a substantial number of missense pathogenic variants occurred in moderately conserved amino acids. Large pathogenic deletions account for about 1% of alleles in patients (Tomatsu et al. 2005; Dung et al. 2013).

The GALNS gene encodes the N-acetylgalactosamine-6-sulfatase enzyme, which catalyzes the hydrolysis of keratan and chondroitin 6-sulfates.

Clinical Sensitivity - Sequencing with CNV PGxome

Using Sanger sequencing, a recent study identified pathogenic variants in 93.6% of the analyzed mutant alleles. Identified pathogenic variants included missense, nonsense, small deletions or insertions, and splice-site mutations (Dung et al. 2013).

Large pathogenic deletions account for about 1% of alleles in patients with identified pathogenic variants (Tomatsu et al. 2005).

Testing Strategy

This test provides full coverage of all coding exons of the GALNS gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

To confirm diagnosis in patients with clinical features and radiological findings suggestive of MPSIV and reduced N-acetylgalactosamine-6-sulfatase enzyme activity with or without increased keratin sulfate and chondroitin-6-sulfate excretion in urine; and potential heterozygous carriers.

Gene

Official Gene Symbol OMIM ID
GALNS 612222
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Morquio Syndrome A AR 253000

Related Test

Name
GM1 Gangliosidosis and Mucopolysaccharidosis Type IVB / Morquio Type B via the GLB1 Gene

Citations

  • Baehner F, Schmiedeskamp C, Krummenauer F, Miebach E, Bajbouj M, Whybra C, Kohlschütter A, Kampmann C, Beck M. 2005. Cumulative incidence rates of the mucopolysaccharidoses in Germany. J Inherit Metab Dis 28: 1011–1017. PubMed ID: 16435194
  • Dung VC, Tomatsu S, Montaño AM, Gottesman G, Bober MB, Mackenzie W, Maeda M, Mitchell GA, Suzuki Y, Orii T. 2013. Mucopolysaccharidosis IVA: correlation between genotype, phenotype and keratan sulfate levels. Mol. Genet. Metab. 110: 129–138. PubMed ID: 23876334
  • Fukuda S, Tomatsu S, Masue M, Sukegawa K, Iwata H, Ogawa T, Nakashima Y, Hori T, Yamagishi A, Hanyu Y. 1992. Mucopolysaccharidosis type IVA. N-acetylgalactosamine-6-sulfate sulfatase exonic point mutations in classical Morquio and mild cases. Journal of Clinical Investigation 90: 1049-1053. PubMed ID: 1522213
  • Hughes DG, Chadderton RD, Cowie RA, Wraith JE, Jenkins JP. 1997. MRI of the brain and craniocervical junction in Morquio’s disease. Neuroradiology 39: 381–385. PubMed ID: 9189888
  • Montaño AM, Tomatsu S, Gottesman GS, Smith M, Orii T. 2007. International Morquio A Registry: clinical manifestation and natural course of Morquio A disease. J. Inherit. Metab. Dis. 30: 165–174. PubMed ID: 17347914
  • Nelson J, Broadhead D, Mossman J. 1988. Clinical findings in 12 patients with MPS IV A (Morquio’s disease). Further evidence for heterogeneity. Part I: Clinical and biochemical findings. Clin. Genet. 33: 111–120. PubMed ID: 3129221
  • Neufeld EF, Muenzer J. 2001. The Mucoploysaccharidoses. 136: 3421-3452.
  • O’Brien JS, Gugler E, Giedion A, Wiessmann U, Herschkowitz N, Meier C, Leroy J. 1976. Spondyloepiphyseal dysplasia, corneal clouding, normal intelligence and acid beta-galactosidase deficiency. Clin. Genet. 9: 495–504. PubMed ID: 817853
  • Solanki GA, Martin KW, Theroux MC, Lampe C, White KK, Shediac R, Lampe CG, Beck M, Mackenzie WG, Hendriksz CJ, Harmatz PR. 2013. Spinal involvement in mucopolysaccharidosis IVA (Morquio-Brailsford or Morquio A syndrome): presentation, diagnosis and management. Journal of Inherited Metabolic Disease 36: 339–355. PubMed ID: 23385297
  • Tomatsu S, Montaño AM, Nishioka T, Gutierrez MA, Peña OM, Tranda firescu GG, Lopez P, Yamaguchi S, Noguchi A, Orii T. 2005. Mutation and polymorphism spectrum of the GALNS gene in mucopolysaccharidosis IVA (Morquio A). Human Mutation 26: 500–512. PubMed ID: 16287098

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.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


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.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: $
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