Prevalence of pyruvate kinase deficiency: A systematic literature review

OBJECTIVES: Pyruvate kinase deficiency (PK deficiency) is a rare disorder caused by compound heterozygosity or homozygosity for > 300 mutations in the PKLR gene. To understand PK deficiency prevalence, we conducted a systematic literature review. METHODS: We queried Embase and Medline for peer‐reviewed references reporting PK deficiency prevalence/incidence, PKLR mutant allele frequency (MAF) among the general population, or crude results from which these metrics could be derived. RESULTS: Of 1390 references screened, 1296 were excluded after title/abstract review; 60 were excluded after full‐text review. Four of the remaining 34 studies were considered high‐quality for estimating PK deficiency prevalence. Two high‐quality studies identified cases from source populations of known sizes, producing estimates of diagnosed PK deficiency prevalence of 3.2 and 8.5 per million. Another high‐quality study derived an estimate of diagnosed PK deficiency prevalence of 6.5 per million by screening jaundiced newborns. The final high‐quality study estimated total diagnosed and undiagnosed PK deficiency prevalence to be 51 per million through extrapolation from observed MAFs. CONCLUSIONS: We conclude that prevalence of clinically diagnosed PK deficiency is likely between 3.2 and 8.5 per million in Western populations, while the prevalence of diagnosed and undiagnosed PK deficiency could possibly be as high as 51 per million.