PF432 EPIDEMIOLOGICAL SHIFT OF GLUCOSE‐6‐PHOSPHATE DEHYDROGENASE (G6PD) MUTATIONS IN NORTHERN ITALY DURING THE LAST 15 YEARS

Background: Glucose‐6‐phosphate dehydrogenase (G6PD) deficiency is an X‐linked recessive hemolytic anemia caused by G6PD gene mutations which affect 400 million people worldwide. To date, more than 140 G6PD mutations have been reported. The distribution and frequency of genetic variants differ depending on ethnicity and geographical areas. Because of new migrations different variants are now present in Europe. Aims: This retrospective study aims to identify variants among the G6PD deficient subjects referred since 2004 to “Ca’ Granda” Foundation Hospital “in Milan. The subjects were divided into 3 groups: group 1 (2004–2008), group 2 (2009–2013) and group 3 (2014–2018).These subjects were studied because of known or suspected G6PD deficiency or for genetic counselling. Methods: The molecular analysis has been carried out by restriction fragments length polymorphisms (RLFP) and direct DNA sequencing. Results: Three hundred and thirty nine G6PD mutated subjects were identified, classified and divided as shown in table 1: Table 1 ‐ G6PD variants identified in glucose 6‐phosphate dehydrogenase‐deficient subjects diagnosed since 2004 (number of subjects with G6PD mutations in italic, percentage % in brackets).During 12 years a significant decrease of the Mediterranean and an important increase of the African, Asian and uncommon variants (classified as Others) have been observed. In the first eight years Cassano and Chatham variants have an increase that does not change in the last four years. During each period new mutations were found: in group 1 the Gly485Asp (c.[1454G> A]) in homozygosity (female), in group 2 the Glu195Arg (c.[584A> G]) in heterozygosity and in group 3 the Ile224Phe (c.[670A>T]) in hemizygosity. Referring to the entire period of the study 2004–2018, in 3 subjects (1.1%) were found Portici variant, responsible for chronic non‐spherocytic haemolytic anaemia, as well as Puerto Limon and Georgia (0,4%). Other variants identified in less than 1% of subjects studied were: Cairo, Mahidol, Ludhiana, Rignano, Santamaria, Sant’Antioco, Canton, Sibari, Cosenza, Abruzzo, Viangchan, Orissa, and Union. Two cases showed the 1365–13T>C polymorphism coupled with 1311C>T variation, generally associated with Mediterranean variant. Summary/Conclusion: These data reflect the appearance of uncommon G6PD mutations in Northern Italy, probably due to new migrations, as consequence G6PD characterization becomes a diagnostic issue. The evidence of polymorphisms in G6PD deficient subjects suggests that not only single variations in the exonic/intronic boundaries, but also specific haplotypes could be causative for G6PD deficiency.