Galactosemia is a potentially lethal, but preventable, disease of newborns. In Phase I of this grant, we demonstrated that a 13C-galactose breath test could be used to assess the degree of impairment of whole body galactose oxidation in more than 90 galactosemic children with a broad spectrum of mutations in the human GALT gene that codes for galactose-l-phosphate uridyltransferase (E C 2 7 7 12). We further demonstrated that this test could be adapted for use in newborn infants with results comparable to those in older children. In Phase II, we will undertake the pre-commercial manufacture and packaging of unit substrate doses for implementation of a field program for secondary screening in the state of Georgia. This program will test the efficacy of outpatient breath testing, using an automated interactive breath collection device and the analysis of breath samples by a new, low-cost mass spectrometer developed for use at the point of care. The results of this crib-side test will be compared with the biochemical and molecular genotyping tests currently used to confirm or deny the diagnosis of infants with an initial positive state-screen test for galactosemia. A rapid assessment of the degree of functional impairment (which is only indirectly predicted from the biochemical and molecular work-up) will enable the physician to differentiate newborns at life-threatening risk from variants of galactosemia before they are exposed to galactose. Implementation of a newly developed 13C-galactose breath test will provide a valuable cost-effective population screening test to measure the degree of impaired galactose metabolism in newborn infants, guide their dietary therapy, and aid in their long-term prognosis.
|Barbouth, Deborah S; Velazquez, Darcy L; Konopka, Stanley et al. (2007) Screening newborns for galactosemia using total body galactose oxidation to CO2 in expired air. Pediatr Res 62:720-4|
|Barbouth, Deborah; Slepak, Tatiana; Klapper, Helene et al. (2006) Prevention of a molecular misdiagnosis in galactosemia. Genet Med 8:178-82|