Ultragenyx and PerkinElmer Genomics have partnered to offer sponsored MPS panel testing to patients who are suspected of having an MPS disorder, or who have been clinically diagnosed with MPS and need confirmatory testing. For Health Care Professionals already familiar with MPS disorders, please use the links below to learn about eligibility, the MPS panel, or to order a collection pack & submit a specimen.

Eligibility

MPS Panel

Order

About MPS

Mucopolysaccharidoses, or MPS disorders, are caused by a deficiency in one of eleven unique lysosomal enzymes (Neufeld & Muenzer, 2014). Each enzyme deficiency affects the breakdown of large long-chain sugars called mucopolysaccharides or glycosaminoglycans, “GAGs” for short. Due to accumulation of GAGs in the lysosomes of cells, these disorders are included in a larger group of disorders known as lysosomal storage diseases or LSDs. The MPS disorders include MPS I (Hurler, Scheie), MPS II (Hunter), MPS III (four subtypes: San Filippo A, B, C, or D), MPS IVA (Morquio A), MPS IVB (Morquio B), MPS VI (Maroteaux-Lamy), MPS VII (Sly), and MPS IX (hyaluronidase deficiency). Many of the signs and symptoms of MPS are very similar between types as the MPS disorders share a common pathophysiological mechanism, the accumulation of un-degraded GAGs in the lysosomes. Symptoms of MPS may include (Lehman, et al., 2011) (Clarke, et al., 2018): skeletal dysplasia, coarse facial features, pulmonary and cardiac symptoms, corneal clouding, hearing loss, joint stiffness or laxity, and dentition abnormalities.

About MPS VII

MPS VII results from an enzyme deficiency in β-glucuronidase (GUS). MPS VII is an autosomal recessive disorder: a copy of a defective GUSB gene that encodes for the GUS enzyme is inherited from each parent. Due to the defect in GUS, GAGs accumulate in the cells leading to multi-systemic disease.

Symptoms of MPS VII may include enlarged spleen and liver, joint stiffness, short stature, and heart/ lung complications. MPS VII may present with a characteristic facial appearance and can lead to progressive skeletal dysplasia. MPS VII patients also can have presentation of cataracts, corneal clouding, hearing loss, developmental delay, and intellectual disability. MPS VII can present at birth with non-immune hydrops fetalis (NIHF) (Montaño, et al., 2016)(Gimovsky, et al. 2014). MPS VII is the most common MPS associated with LSD-based NIHF (Vianey-Saban, et al., 2016).

Incidence
All MPS disorders have an estimated combined incidence of 1 in 25,000 (Tomatsu, et al., 2013) (Khan, et al., 2017). MPS VII is a rare disorder with a variable frequency of disease depending on geographical origin and is likely under-recognized (Montaño, et al., 2016).

For providers from New York State, please see additional ordering information for New York State.

New York Testing

New York State Public Health Law and Regulations require samples that are collected from patients within New York State be tested by a clinical laboratory that holds proper New York licensing. Due to the rarity of many genetic conditions, laboratories may not hold proper licensing for all testing options available. However, there can be justification for requesting laboratory testing from a facility that does not hold the specific disease testing permits.

In these instances, a Non-Permitted Laboratory Test Request can be submitted to the New York State Health Department for approval. Approval must be granted prior to submitting and testing a sample collected in New York to the non-permitted laboratory. Approval or rejection will be sent in writing to the submitting physician for each request submitted to the department. If the request is rejected, the reason for rejection will be included in the response.

For Non-Approved Tests

For patients residing in New York State, the following form will need to be completed, submitted and approved by New York State Department of Health prior to submitting a specimen for testing. Once approved, you may submit the patient specimen, test requisition form, and New York approval letter to initiate testing.

Eligibility

Symptoms consistent with MPS VII or another MPS disorder.

Program

Ultragenyx is partnering with PerkinElmer to offer sponsored, no-charge testing for MPS. This sponsored program uses dried blood spot punches to measure enzyme deficiency from an MPS enzyme panel and in cases of β-glucuronidase deficiency, GUSB gene sequencing is performed.

Patients suspected of having an MPS disorder

  1. MPS enzyme panel. If β-glucuronidase is deficient, proceed to:
  2. GUSB DNA sequencing analysis (with copy number variant analysis if needed)

MPS Panel

MPS Enzyme Panel
MPS I α-L-iduronidase
MPS II iduronate-2-sulfatase
MPS IIIB α-N-acetylglucosaminidase
MPS IVA N-acetyl galactosamine-6-sulfatase
MPS IVB β-galactosidase
MPS VI N-acetylglucosamine-4-sulfatase
MPSVII (Sly Syndrome) β-glucuronidase

Specimen for MPS Panel and Sequencing

Dried Blood Spot

Methodology

Flow Injection Tandem Mass Spectrometry (FIA/MS/MS)

GUSB gene sequencing methodology: performed via NGS analysis if β-glucuronidase is deficient. All coding exons and immediate flanking intronic regions of the gene are sequenced. Copy number variation (CNV) is assessed using Biodiscovery’s NxClincal software and is designed to detect deletions and duplications of three exons or more.

FOLLOW US

Ordering Instructions

Request a PerkinElmer Genomics test pack or contact PerkinElmer client services at +1-866-354-2910 to request a collection pack.

Download and review the step-by-step instructions to collect a DBS sample.

Specimen: Dried blood spot (DBS)

To place a paper order, use the Ultragenyx Sponsored MPS Testing Requisition form in the PerkinElmer Genomics test pack or download the Ultragenyx Sponsored MPS Testing Requisition Form.

  1. Fill in the patient information and the HCP Provider information.
  2. Under Billing Information, leave fields blank.
  3. Sign the Physician Statement.
  4. Complete the Clinical History page by selecting relevant clinical history/symptoms.
  5. Ensure that the patient has signed the informed consent form.

For providers from New York State, please see additional ordering information for New York State.

For more ordering information contact PerkinElmer client services at +1-866-354-2910

Download and review the step-by-step instructions to collect a DBS sample.

Label the patient DBS specimen card with the patient name and date of birth.

Contact PerkinElmer client services at +1-866-354-2910 for questions.

Place the following in the PerkinElmer Genomics pre-paid return envelope:

  1. Labeled patient DBS specimen card
  2. Completed Ultragenyx Sponsored MPS Testing Requisition Form with signed Physician Statement and completed Clinical History page.
  3. Patient-signed informed consent form.

For samples that are collected not utilizing the PerkinElmer Genomics test pack: ship sample, Ultragenyx MPS Sponsored Testing Requisition Form, and patient informed consent form by preferred shipping method to PerkinElmer Genomics at PerkinElmer Genetics 250 Industry Dr. Suite 400 Pittsburgh, PA 15275, USA

As a patient’s clinical presentation is an essential part of fully interpreting genetic test results, we ask that you kindly include any applicable medical records or clinical notes with the sample at the time of test submission.

Results:
Once PerkinElmer MPS panel assay results are available, you will receive phone call to report abnormal findings, with a written report to follow within the established turnaround time for the ordered test.

Turn-Around-Times (TATs)
MPS Enzyme Assay: 3 days GUSB Gene Sequencing (If β-glucuronidase is deficient): 3 Weeks

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Disclaimer
While Ultragenyx provides financial support for this program, healthcare professionals must confirm that patients meet certain criteria to use the program and shall not seek reimbursement for the testing or services provided under this program from any third party, including but not limited to federal healthcare programs.  Ultragenyx receives de-identified/anonymized data from this program, but at no time does Ultragenyx receive patient-identifiable information. Healthcare professionals who use this program have no obligation to recommend, purchase, order, prescribe, promote, administer, use, or support any Ultragenyx product.

About Ultragenyx Pharmaceutical Inc.
Ultragenyx is a biopharmaceutical company committed to bringing to patients novel products for the treatment of serious rare and ultra-rare genetic diseases. The company has built a diverse portfolio of approved therapies and product candidates aimed at addressing diseases with high unmet medical need and clear biology for treatment, for which there are no approved therapies.

The company is led by a management team experienced in the development and commercialization of rare disease therapeutics. Ultragenyx’s strategy is predicated upon time- and cost-efficient drug development, with the goal of delivering safe and effective therapies to patients with the utmost urgency.

References
Clarke, L., Ellaway, C., Foster, H. C., Giugliani, R., Goizet, C., Goring, S., . . . Wijburg, F. (2018). Understanding the Early Presentation of Mucopolysaccharidoses Disorders: Results of a Systematic Literature Review and Physician Survey. Journal of Inborn Errors of Metabolism6, 1-12. doi:10.1177/2326409818800346

Gimovsky, A. C., Luzi, P., & Berghella, V. (2015, March). Lysosomal storage disease as an etiology of nonimmune hydrops. American Journal of Obstetrics and Gynecology212(3), 281-290. doi:10.1016/j.ajog.2014.10.007

Khan, S. A., Peracha, H., Ballhausen, D., Wiesbauer, A., Rohrbach, M., Gautschi, M., . . . Tomatsu, S. (2017). Epidemiology of mucopolysaccharidoses. Molecular Genetics and Metabolism121, 227-240. doi:10.1016/j.ymgme.2017.05.016

Lehman, T. J., Miller, N., Norquist , B., Underhill, L., & Keutzer, J. (2011, Dec). Diagnosis of the mucopolysaccharidoses. Rheumatology supplement50(Suppl_5), v41-v48. doi:10.1093/rheumatology/ker390

Montaño , A. M., Lock-Hock, N., Steiner, R. D., Graham, B. H., Szlago, M., Greenstein, R., . . . Sly, W. S. (2016, June). Clinical course of sly syndrome (mucopolysaccharidosis type VII). Journal of Medical Genetics53(6), 403-418. doi:10.1136/jmedgenet-2015-103322

Neufeld, E. F., & Muenzer, J. (2014). “The Mucopolysaccharidoses.” The Online Metabolic and Molecular Bases of Inherited Disease. (D. Valle, A. L. Beaudet, B. Vogelstein, K. W. Kinzler, S. E. Antonarakis , A. Ballabio, . . . G. Mitchell, Eds.) New York, NY: McGraw Hill. Retrieved from https://ommbid.mhmedical.com/content.aspx?bookid=971&sectionid=62642135

Tomatsu, S., Fujii, T., Fukushi, M., Oguma, T., Shimada, T., Maeda, M., . . . Orii, T. (2013, Sep-Oct). Newborn screening and diagnosis of mucopolysaccharidoses. 110(1-2), 42-53. doi:10.1016/j.ymgme.2013.06.007

Vianey-Saban, C., Acquaviva, C., Cheillan, D., Collardeau-Frachon, S., Guibaud, L., Pagan, C., . . . Froissart, R. (2016, July 8). Antenatal manifestations of inborn errors of metabolism: biological diagnosis. Journal of Inherited Metabolic Disorders39, 611–624. doi:https://doi.org/10.1007/s10545-016-9947-8|

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MRCP-UX003-00243 03/2020