Pyruvate kinase deficient hemolytic anemia in the Northern Irish population

Abstract

A common cause of hereditary nonspherocytic hemolytic anemia is pyruvate kinase deficiency, which is associated with lifelong chronic hemolysis. Pyruvate kinase deficiency has a worldwide distribution with a higher prevalence in the Caucasian population, and especially in Europe and North America. It is inherited in an autosomal fashion and over 180 different mutations have been described. Investigation of hemolytic anemia in Northern Ireland has uncovered 4 new cases of pyruvate kinase deficiency. Molecular investigation revealed a total of six different mutations. One mutation (p.Arg495Val) is reported here for the first time in a homozygous patient. Another mutant PKLR allele harbored a nonsense and frameshift mutation in cis: c.[721G>T; 826delG]. Considering the three previously described Irish cases of pyruvate kinase deficiency, this study raises the total number of pyruvate kinase-deficient Irish patients to seven in which a total of nine mutant PKLR alleles were identified. This indicates the absence of a founder pyruvate kinase mutation in the Northern Ireland population. Although pyruvate kinase deficiency is prevalent in the Caucasian population it is not reflected in the number of individuals diagnosed in Northern Ireland. Hence, many cases of pyruvate kinase deficiency may remain undetected possibly due to the resultant anemia being mild.