Classic galactosemia is an autosomal recessive disorder of carbohydrate metabolism, due to a severe deficiency of the
enzyme,
galactose-1-phosphate uridyltransferase (GALT), that catalyzes the conversion of
galactose-1-phosphate and
uridine diphosphate glucose (UDPglucose) to
uridine diphosphate galactose (UDPgalactose) and
glucose-1-phosphate. Upon consumption of
lactose in the neonatal period, the affected infants develop a potentially lethal disease process with multiorgan involvement. Since the advent of newborn screening (NBS) for
galactosemia, we rarely encounter such overwhelmingly ill newborns. After ascertainment that the positive NBS indicates the possibility of
galactosemia due to
GALT deficiency, the critical question for the physician is whether the infant has the classic or a variant form of
GALT deficiency, as
classic galactosemia is a medical emergency. However, there are over 230 GALT gene mutations that have been detected around the world. Yet, most positive NBS tests are due to the Duarte biochemical variant condition or a simple false positive. In order to make the correct decision as well as provide informative counseling to parents of infants with a positive NBS, I utilize a relatively simple classification scheme for
GALT deficiency. There are three basic forms of
GALT deficiency: 1)
classic galactosemia; 2) clinical variant
galactosemia; and 3) biochemical variant
galactosemia. The classic genotype is typified by Q188R/Q188R, the clinical variant by S135L/S135L and the biochemical variant by N314D/Q188R. In
classic galactosemia, the erythrocyte GALT
enzyme activity is absent or markedly reduced, the blood
galactose and erythrocyte
galactose-1-
phosphate levels are markedly elevated, and the patient is at risk to develop potentially lethal E. coli
sepsis, as well as the long-term diet-independent complications of
galactosemia. Patients with the clinical variant form require treatment but do not die from E. coli
sepsis in the neonatal period. If the clinician suspects
galactosemia, even if based on clinical findings alone, then the infant should be immediately placed on a
lactose-restricted diet. The purpose of this review is to help the clinician make the correct therapeutic decision after an NBS test has returned positive for
galactosemia.