Molecular characterization of glucose-6-phosphate dehydrogenase deficiency in Turkey.

Sir, Red cell glucose-6-phosphate dehydrogenase (G6PD) deficiency is not rare in Turkey. The frequency of this enzyme deficiency in Turkish males was reported to vary between 0.5-11.4% depending upon geographical areas and/or ethnic groups.1,2 Molecular studies of red cell G6PD enzyme revealed the presence of about 122 mutations which were recently reviewed by Vulliamy et al.3 Enzyme deficiency in Turkey is rarely associated with chronic hemolytic anemia with only one such subject having been reported. In this patient, enzyme deficiency resulted from the 823G mutation.4 No detailed molecular study has been conducted in Turkey to search for the frequency of polymorphic deficient mutations. The study presented below was designed in order to fill this gap. A total of 50 unrelated male subjects with red cell G6PD deficiency were the subjects of this study. Subjects were referred to our center from various parts of Turkey. The diagnosis of enzyme deficiency was made in the neonatal period in 40 of 50 subjects during screening studies for hyperbilirubinemia. In the remaining 10 subjects, enzyme deficiency was diagnosed at the time of a hemolytic crisis. Genomic DNA was obtained from peripheral blood using standard methods. PCR was used to amplify the portions of coding region of the G6PD gene as described previously.5 All DNA samples were screened for common known mutations by using appropriate restriction endonuclease enzymes.6 For mutations which could not be determined by restriction endonuclease analyses such as G-A at nt 202 and G-A at nt 1003 (Chatam), direct sequencing of PCR products was performed. The study revealed that the enzyme deficiency was associated with Mediterranean type of G6PD deficiency B– (563T) in 40 of 50 subjects (80%), two patients had A-(376G/202A) type of G6PD deficiency (4%) and one patient had 1003 A mutation (G6PD Chatam)(2%). In the remaining 7 subjects (14%) none of the above mentioned mutations was found to be responsible for the deficiency (Table 1). Two patients with A– were living in different villages in the region of Ankara. Our study indicated that although the major molecular pathology in G6PD deficiency is G6PD B– (563T), G6PD A– (376G/202A) and G6PD Chatam (1003A) mutations are also present in the Turkish population. Population screening studies showed that the frequency of G6PD enzyme deficiency was 6.5-11.4% in Çukurova region where HbS of Benin type is also prevalent.1,2,7 Therefore, one may expect G6PD deficiency of A– to be present in this population. Contrary to this expectation, none of the A– patients originated from this region suggesting that G6PD mutation had occurred sometime after the introduction of the HbS gene into this population. The presence of isolated G6PD A– in central Anatolia indicates that in Turkey, like other Mediterranean countries, the African G6PD genes were introduced by slavery and not by large population movements. G6PD Chatam was diagnosed in a patient from central Anatolia. This pathology was first diagnosed in Asian Indians followed by a Syrian and later in several Mediterranean countries.8 It seems that this mutation is the third most common polymorphic deficiency mutation after B– and A– in Mediterranean countries.