Current population-based newborn screening for galactosemia relies on red blood cell assay of galactose oxidation, but identification of galactose uridyl transferase (GALT) mutations does not differentiate between patients who will respond to dietary therapy and those who will not. Our studies of the Q188R and S135L mutations using whole body 1-13C-galactose oxidation (WBGO) to CO2 have indicated organ-specific differences in expression of these two genes. S135L and Q188R patients both lack RBC activity, but S135L patients have virtually normal WBGO levels and a relatively favorable developmental outcome. This discovery suggests that mapping of WBGO activity in selected genotypically and phenotypically characterized patients could lead to a functional correlation between mutations, WBGO and outcome. In Phase I, we will study WBGO in 18 well- characterized patients representing single and compound mutations. In order to begin assessment in the newborn infant, adaptations will be made to existing Meretek Diagnostics breath test kit components and validated for use in a general clinical setting. We will develop a WBGO protocol for population-based screening of GALT-deficient infants and for an expanded retrospective assessment of known probands to be completed in Phase II.Proposed commercial application:Development of a 13C galctose breath test will provide a valuable cost-effective population-based screening test to assess galactosemic impairment in newborn infants and guide their dietary therapy.National Institute fo General Medical Sciences (NIGMS)
