Clinical Information

Galactosemia is an autosomal recessive disorder that results from a deficiency of any 1 of the 4 enzymes catalyzing the conversion of galactose to glucose: galactose-1-phosphate uridyltransferase (GALT), galactokinase (GALK), uridine diphosphate galactose-4-epimerase (GALE), and galactose mutarotase (GALM).

Epimerase deficiency galactosemia can be categorized into 3 types: generalized, peripheral, and intermediate. Generalized epimerase deficiency galactosemia is rare with less than 10 cases described in the literature and results in profoundly decreased enzyme activity in all tissues, whereas peripheral epimerase deficiency galactosemia results in decreased enzyme activity in red and white blood cells, but normal enzyme activity in all other tissues. This is compared to intermediate epimerase deficiency galactosemia, which results in decreased enzyme activity in red and white blood cells and less than 50% of normal enzyme levels in other tissues.

Clinically, infants with generalized epimerase deficiency galactosemia develop symptoms such as liver and kidney dysfunction and mild cataracts when on a normal milk diet, while infants with peripheral or intermediate epimerase deficiency galactosemia do not develop any symptoms. Generalized epimerase deficiency galactosemia is treated by a galactose- and lactose-restricted diet, which can improve or prevent the symptoms of kidney and liver dysfunction and mild cataracts. Despite adequate treatment from an early age, individuals with generalized epimerase deficiency galactosemia remain at increased risk for developmental delay and intellectual disability. Unlike patients with classic galactosemia resulting from a GALT deficiency, female patients with generalized epimerase deficiency galactosemia experience normal puberty and are not at increased risk for premature ovarian failure. Based upon reports by newborn screening programs, the frequency of epimerase deficiency galactosemia in the United States ranges from approximately 1 in 6700 African American infants to 1 in 70,000 infants of European ancestry.

Galactose-1-phosphate (Gal1P) accumulates in the erythrocytes of patients with galactosemia due to either GALT or GALE deficiency or in neonates with GALM deficiency. The quantitative measurement of Gal1P (GAL1P / Galactose-1-Phosphate, Erythrocytes) is useful for monitoring compliance with dietary therapy. Gal1P is thought to be the causative factor for development of liver disease in patients with GALT or GALE deficiency. Because of this, patients should maintain low levels and be monitored on a regular basis.

Newborn screening varies from state to state and identifies potentially affected individuals by measuring total galactose (galactose and Gal1P) or determining the activity of the GALT enzyme. The diagnosis of galactosemia is established by follow-up quantitative measurement of GALT enzyme activity. If enzyme levels are normal, but an infant has an elevated Gal-1-P, then epimerase deficiency galactosemia should be considered. Molecular analysis of the GALE gene is available; order CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies and specify Gene List ID: IEMCP- MGXGL2.

For more information see Galactosemia Testing Algorithm.