The global prevalence and genetic spectrum of primary carnitine deficiency

Abstract

Background Primary carnitine deficiency (PCD) is an autosomal recessive rare disorder of carnitine cycle and carnitine transport caused by mutations in the SLC22A5 gene. The prevalence of PCD is unclear. This study aimed to estimate the carrier frequency and genetic prevalence of PCD using Genome Aggregation Database (gnomAD) data. Methods The pathogenicity of SLC22A5 variants was interpreted according to the American College of Medical Genetics and Genomics (ACMG) standards and guidelines. The minor allele frequency (MAF) of the disease-causing variants of the SLC22A5 gene in 807,162 individuals was examined to estimate the global prevalence of PCD in five major ethnicities: African (afr), Admixed American (amr), East Asian (eas), Non-Finnish European (nfe) and South Asian (sas). The global and population-specific carrier frequencies and genetic prevalence of PCD were calculated using the Hardy–Weinberg equation. Results Total of 195 pathogenic/likely pathogenic variants (PV/LPV) of the SLC22A5 gene were identified according to the ACMG standards and guidelines. The global carrier frequency and genetic prevalence of PCD were 1/88 and 1/31,260, respectively. Conclusions The prevalence of PCD is estimated to be 1/30,000 globally, with a range of between 1/20,000 and 1/70,000 depending on ethnicity.