This article includes discussion of galactosemia, classic galactosemia, galactose-1-phosphate uridyltransferase (GALT) deficiency, transferase deficiency, UTP-hexose-1-phosphate-uridyltransferase deficiency, UDPgalactose 4'-epimerase (GALE) deficiency, and galactokinase (GALK) deficiency. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.
Hereditary galactosemia due to galactose-1-phosphate uridyltransferase (GALT) deficiency is 1 of the inborn errors of carbohydrate metabolism and can be a life-threatening illness during the newborn period. First described in the United States literature in a variant patient in 1935 by Mason and Turner, galactose-1-phosphate uridyltransferase (GALT) deficiency is the most common enzyme deficiency that causes clinically relevant hypergalactosemia. Removing lactose by stopping breast milk or proprietary formula feedings largely eliminates the toxicity associated with newborn disease, but long-term complications almost always occur in the severe form of GALT deficiency, as reported by Komrower and Lee in 1970, Fishler and colleagues in 1980, and, most convincingly, in the 1990 retrospective survey by Waggoner and colleagues. In this article, the author reviews the clinical, laboratory, and imaging features of this enigmatic disease, including putative biochemical toxicities that center around galactose-1-phosphate and galactitol metabolism.
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• Galactosemia is a medical emergency in the newborn period.
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• Dietary lactose restriction usually rescues affected newborn infants, preventing multiorgan toxicity syndrome and eliminating E coli sepsis.
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• Prospective dietary therapy does not prevent long-term CNS complications nor does it prevent primary ovarian insufficiency in affected women.
Historical note and terminology
The first report of galactosemia was that of von Reuss in 1908 (123). It concerned an infant on breast milk with poor growth. In 1917, Goppert reported an infant with poor growth, lactose exposure, and hypergalactosuria (42). The first comprehensive description of the variant form of hereditary galactosemia in 1935 by Mason and Turner was of an African-American infant (82). It was also the first report of a patient with any form of galactosemia due to GALT deficiency in the American literature. This patient had not been placed on a lactose-restricted diet until 10 months of age. The diet treatment relatively quickly reversed the complications of poor growth, developmental delay, liver disease, and anemia. It is not surprising that more infants with classic galactosemia were not described by 1935 because it is thought that most untreated babies die of E coli sepsis in the newborn period (09).