Purpose: To establish the incidence and molecular basis of type II galactosemia in Indian infants presenting with congenital cataracts.
Methods: 200 infants with congenital cataracts were screed for galactokinase (GALK) enzyme deficiency. GALK enzyme activity was measured using radioactive galactose-1-(14)C and mutations were studied using polymerase chain reaction (PCR), single strand conformational polymorphism (SSCP) and subsequent DNA sequencing.
Results: 16 (8%) out of 200 infants with congenital cataracts were found to be GALK deficient with male: female:: 9:7. A significantly reduced GALK activity of 0.13 ± 0.04 µmoles/h/mL was observed in the galactosemia patients compared to 0.232 ± 0.07 µmoles/h/mL in the normal controls. A total of 5 distinct mutations were identified in GALK gene in five different patients out of which four were novel mutations viz. S79F, S79Y, S205S and F275Y. The functional significance of the mutations and splicing defects associated with them were investigated using different computer based applications.
Conclusion: The study highlighted the importance of GALK gene analysis in diagnosis of galactosemia in Indian population. It also revealed that the mutational profile of Indian GALK patients differs significantly from other populations studied. Low mutation detection rate observed in this study may be due to the fact that SSCP is a quite indirect and non-fullproof method of mutation detection.