Glucose-6-phosphate dehydrogenase (G6PD; E.C. 220.127.116.11) deficiency is the commonest inborn error of metabolism with more than 140 genetic variants. The incidence of G6PD deficiency is 2–9% in Pakistan, but G6PD variants were never studied comprehensively. We therefore designed this study to describe the frequency of G6PD variants and their associated enzyme activities in Pakistan.Methods:
Patients diagnosed with G6PD deficiency were enrolled. RFLP-PCR was utilized to identify common mutations previously reported from Asian countries. Where mutational analysis failed, amplification of 9–12 exons with subsequent gene sequencing was performed. G6PD enzyme activity was assessed through the quantitative enzyme assay.Results:
Two hundred and seventy-six G6PD-deficient subjects (237 male and 39 women) were investigated. G6PD Mediterranean (563C-T) was the most common genetic variant (n = 216 or 78%). G6PD Chatham (1003A-G) and G6PD Orissa (131C-G) were observed in 14 (5%) and two (0.7%) subjects respectively. A novel mutation 973 G-A with a predicated amino acid change of asp325asn was identified in exon 9. This was named G6PD Karachi after the place of origin of proband. Polymorphism in position 1311C/T was uniformly observed with all variants. Forty-three or 17% of DNA samples remained uncharacterized. Very low levels of G6PD enzyme activity was observed with 563C-T mutation.Conclusion:
We concluded that 563C-T was the commonest G6PD variant, while 1003A-G and 131C-G were less-frequent genetic variants of G6PD in Pakistani population. A novel genetic variant 973G-A was also identified. Very low levels of G6PD enzyme activity was seen with G6PD 563C-T. Mutational analysis failed in a significant proportion of samples warranting further work.