Early cataract formation due to galactokinase deficiency: impact of newborn screening

Galactokinase (GALK) deficiency is an autosomal recessive disorder causing cataract formation that can be prevented or mitigated by early diagnosis and galactose-restricted diet. The aim of this retrospective study was to explore whether GALK-deficiency meets the criteria for neonatal mass screening programs.

From 2000 until 2010, the Screening Laboratory Hannover performed newborn screening in 1,950,927 infants from Germany for galactosemia by measuring galactose-1-phosphate-uridyl-transferase and total galactose concentration (free galactose plus galactose-1-phosphate), including automatic screening for GALK deficiency.

Eleven cases were found with elevated galactose levels accompanied by normal transferase activity. Nine of 11 cases were informative; the diagnosis was established by demonstrating deficient activity of the GALK enzyme in erythrocytes. To our knowledge, screening did not produce any false negative results. All patients were treated with a galactose-restricted diet from the neonatal period or infancy. Three of nine patients suffered from congenital cataracts or eventual development of cataracts, despite normal galactose concentrations in blood.

Newborn screening for GALK deficiency prevents or at least mitigates cataract formation. As screening for GALK deficiency is technically simple, it seems to be reasonable to include this disorder in routine screening programs by simultaneous determination of transferase activity and quantification of galactose plus galactose-1-phosphate in dried blood spots.