Estimating the prevalence of pyruvate kinase deficiency from the gene frequency in the general white population.

Pyruvate kinase (PK) deficiency is the most common cause of hereditary nonspherocytic hemolytic anemia. The prevalence of this deficiency is unknown, though some estimates have been made based on the frequency of low red cell PK activity in the population. An additional 20 patients with hereditary nonspherocytic hemolytic anemia caused by PK deficiency have been genotyped. One previously unreported mutation 1153C-->T (R385W) was encountered. The relative frequency of PK mutations in patients with hemolytic anemia caused by PK deficiency was calculated from the 18 white patients reported here and from 102 patients previously reported in the literature. DNA samples from 3785 subjects from different ethnic groups have been screened for the 4 more frequently encountered mutations-c.1456 C-->T(1456T), c.1468 C-->T(1468T), c.1484 C-->T(1484T), and c.1529 G6A (1529A)-by allele-specific oligonucleotide hybridization. Among white patients the frequency of the 1456T mutation was 3.50 x 10(-3); that of the 1529A mutation was 2.03 x 10(-3). Among African Americans the frequency of the 1456T mutation was 3.90 x 10(-3) The only mutation found in the limited number of Asians tested was 1468T at a frequency of 7.94 x 10(-3). Based on the gene frequency of the 1529A mutation in the white population and on its relative abundance in patients with hemolytic anemia caused by PK deficiency, the prevalence of PK deficiency is estimated at 51 cases per million white population. This number would be increased by inbreeding and decreased by failure of patients with PK deficiency to survive.