Rapid Carrier and Newborn Diagnostic Testing for MSUD

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Maple Syrup Urine Disease (MSUD) is a recessive genetic disorder resulting from defects in the branched chain a-keto acid dehydrogenase complex (BCKAD). Infants with classic MSUD appear normal at birth, but can die within 2-3 weeks if untreated. Although generally rare (1:200,000 births), the incidence of MSUD in certain Mennonite communities is quite high (1:176 live births), and results from a specific defect (Y393N) in the BCKAD E1a subunit gene. Although early detection and treatment are critical to favorable prognosis for MSUD patients, there is no commercial or state DNA testing available. Newborn screening by serum amino acid analyses occurs in only 23 states, and requires that testing be delayed until branched chain amino acids accumulate, increasing an infant's risk of neurological damage. At the request of two Mennonite communities we developed a DNA-based test for carrier and newborn screening. Unfortunately, it is not feasible for an academic research laboratory to maintain this test, nor is the current test optimal for commercial use. We propose a collaborative effort with Paternity Testing Corporation to apply two novel approaches, denaturing high-performance liquid chromatography and molecular beacons, to developing an improved rapid, sensitive and commercially applicable test for the Y393N E1a gene defect. PROPOSED COMMERCIAL APPLICATIONS: A commercially available genetic test for MSUD would play a vital role in improving prognosis and outcomes for families affected by this orphan disease, especially in the Mennonite community. While not a highly profitable venture in itself, such a test fulfills an important need to the community, and will pave the way for developing analogous tests for other neglected orphan diseases.