Galactosemia is an autosomal recessive metabolic disorder that occurs due to galactose-1-phosphate uridyl transferase enzyme deficiency that leads to hepatic, ophthalmic, neural, and renal derangements. Inborn error of metabolism with the inability to metabolize galactose appropriately. This results in toxic effects on brain, liver, kidney, and eyes. Early diagnosis and galactose-free diet are the keys to the limitation of the symptoms of the disease.
Galactose-1-Phosphate Uridyltransferase Deficiency; GALT Deficiency.
Friedrich Goppert (1870-1927), a German physician, first described the disease in 1917. The defect in galactose metabolism was identified by a group led by Herman Kalckar in 1956.
The incidence in the general population is estimated between 1:30,000 and 1:70,000, with the highest incidence in Ireland. Galactosemia is about one hundred times more common (1:480 births) within the population. Its incidence is about 1 per 60,000 births for people of European ancestry. It occurs in all races, but the incidence is lower among Asian people. Both genders are equally affected.
Transmission is autosomal recessive. The responsible gene encoding galactose-1-phosphate uridyltransferase (GALT) has been mapped to 9p13.
Lactose is a disaccharide consisting of galactose and glucose that is metabolized to glucose-6-phosphate via uridine diphosphate (UDP)-glucose in the Leloir pathway. Three different enzyme defects within the Leloir pathway can lead to galactosemia. Classic galactosemia, the most common form, is caused by GALT deficiency. The inability to metabolize galactose-1-phosphate to UDP-galactose results in accumulation of the former in brain, kidney, and liver, where it exerts a toxic effect. Galactosemia also can be caused by a deficiency in galactokinase, the enzyme responsible for the initial phosphorylation of galactose to galactose-1-phosphate. Erythrocytic galactokinase activity (used for diagnostic purposes) is significantly diminished in homozygous patients, whereas intermediate activities are measured in heterozygous children. Increased galactose levels are found in blood and urine samples after ingestion of lactose. In general, the prognosis is better than observed for the classic form. Finally, UDP-galactose-4-epimerase is necessary for the conversion of UDP-galactose to UDP-glucose.The deficiency of this enzyme comes in two different clinical forms. The benign form usually is detected during newborn screening tests with increased levels of erythrocytic galactose-1-phosphate concentrations, whereas galactokinase and uridyltransferase activities are normal. In this benign form, the defect affects only blood cells, so no treatment is required. In the generalized form, however, the clinical course is indistinguishable from classic galactosemia. In patients with black ethnic background, the most frequent mutation (S135L, which was previously called “Negro” or “African American” variant) accounts for approximately 45% of the mutant alleles. Homozygosity for the S135L allele and for two other mutant alleles (Duarte and Los Angeles variants) results in approximately 50% of normal GALT activity and a mild clinical ...