Screening newborns for galactosemia using total body galactose oxidation to CO2 in expired air

Classic galactosemia is caused by impaired galactose-1-phosphate uridyltransferase (GALT EC 2.7.712). If discovered and treated within the first days of life, the acute problems of hepatocellular damage, sepsis, and death are prevented. However, chronic problems such as ataxia, tremor, dyspraxic speech, and ovarian failure may occur. To determine whether screening newborns before discharge from the nursery for GALT deficiency is feasible and whether acute and chronic signs could be prevented by earlier intervention, we developed a simplified “breath test.” We quantitated total body oxidation of 13C-D-galactose to 13CO2 in expired air by normal newborns between 2 h and 2 mo of age and compared their results to older children with GALT deficiency. We found no differences in total body galactose oxidation (TBGO) among normal newborns up to 48 h of age, but a 2-fold rise in TBGO developed during their first 2 wk of life. Older children with galactosemia had significantly less oxidative capacity than normal newborns. We conclude that newborn breath testing for total body galactose oxidation is feasible before discharge from nursery. It has potential utility for both preventing acute neonatal toxicity and determining the mechanisms producing long-term complications such as ovarian failure, dyspraxia, ataxia, and tremors.