PB1974 PYRUVATE KINASE DEFICIENCY IN FOUR CHILDREN WITH TWO UNPUBLISHED MUTATIONS

Background:Pyruvate kinase is a key enzyme of anaerobic glycolysis which helps keeping the energy level of red blood cells and their viability in circulation. The genetic heterogeneity of pyruvate kinase deficiency (PKD) is high and, to this day, over 250 different mutations have been identified.Aims:We aimed to emphasize the importance of genetic testing in patients with unexplained non‐immune hemolytic anemia.Methods:Four patients who had been followed because of non‐spherocytic hemolytic anemia and in whom no causative enzyme deficiencies were identified were referred for targeted next‐generation sequencing using the Oxford Red Cell Panel, a 50‐gene panel for inherited anemias.Results:We studied four patients (2 females, and 2 males) with evidence of chronic hemolytic anemia aged between 4 years and 24 years. Three of the four patients had jaundice, pallor and hepatosplenomegaly, while one patient had growth retardation and hypotonicity. One patient had gallstones and also undergone splenectomy at the age of two. While homozygous mutation was detected in three of four patients, only one patient had a compound heterozygous mutations (c.602G > A, c.1675C > G). The five identified mutations are single nucleotide gene changes. Two of the five mutations (c.602G > A, and c.172C > T) are previously unpublished.Summary/Conclusion:The clinical presentation of PKD ranges from frequent transfusion in neonates to mild jaundice in adulthood. Total pyruvate kinase in liver and red cell (PKLR) gene sequencing is necessary for the characterization of all patients with PKD and for genetic counselling. We also report two previously unpublished mutations in PKLR.