Classic Galactosemia: Study on the Late Prenatal Development of GALT Specific Activity in a Sheep Model

Classic galactosemia results from deficient activity of galactose-1-phosphate uridylyltransferase (GALT), a key enzyme of galactose metabolism. Despite early diagnosis and early postnatal therapeutic intervention, patients still develop neurologic and fertility impairments. Prenatal developmental toxicity has been hypothesized as a determinant factor of disease. In order to shed light on the importance of prenatal GALT activity, several studies have examined GALT activity throughout development. GALT was shown to increase with gestational age in 7-28 weeks human fetuses; later stages were not investigated. Prenatal studies in animals focused exclusively on brain and hepatic GALT activity. In this study, we aim to examine GALT specific activity in late prenatal and adult stages, using a sheep model. Galactosemia acute target-organs-liver, small intestine and kidney-had the highest late prenatal activity, whereas the chronic target-organs-brain and ovary-did not exhibit a noticeable pre-or postnatal different activity compared with nontarget organs. This is the first study on GALT specific activity in the late prenatal stage for a wide variety of organs. Our findings suggest that GALT activity cannot be the sole pathogenic factor accounting for galactosemia long-term complications, and that some organs/cells might have a greater susceptibility to galactose toxicity. (C) 2017 Wiley Periodicals, Inc.