Classic galactosemia: dietary dilemmas

Classic galactosemia (McKusic 230400) is an inborn error of galactose metabolism caused by a deficiency of the enzyme galactose-1-phosphate uridyltransferase (GALT, EC 2..7.712), resulting in accumulation of the metabolites galactitol and galactose-1-phosphate. Patients ingesting galactose from breast milk or infant formula present in the first weeks of life with feeding difficulties, hepatocellular dysfunction, hypoglycemia, renal tubular dysfunction, cataract, and sepsis. Immediate removal of galactose from the diet results in a full recovery from this life-threatening neonatal crisis (Holton et al. 2001; Bosch 2006). Mason and Turner (1935) were the first to report the successful use of a milk-free diet in an infant with galactosemia. In the 1950s, different strategies to feed infants a diet without galactose were discussed in the literature (Salt et al. 1955; Jones and Leak 1959). Nowadays, initiating the diet is much easier, as infant formulas with a very limited amount of galactose are widely available. Still, there are dilemmas in the treatment of galactosemia, and the dietary treatment varies widely around the world. The most troubling issue is that despite a continued galactose-restricted diet, and irrespective of a neonatal crisis, many patients suffer from long-term complications, such as reduced cognitive ability, language impairment, decreased bone mass, and hypergonadotrophic hypogonadism in women (Kaufman et al. 1981; Waggoner et al. 1990; Schweitzer et al. 1993; Panis et al. 2004; Potter et al. 2008; Schadewaldt et al. 2010).