The global prevalence and genetic spectrum of primary carnitine deficiency

Abstract

AbstractBackgroundPrimary 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.MethodsThe 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 SLC22A5 gene disease-causing variants in 807,162 unique 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.ResultsIn total, 195 pathogenic/likely pathogenic variants (PV/LPV) were identified according to ACMG standards and guidelines. The global carrier frequency and genetic prevalence of PCD were 1/88 and 1/31,260, respectively.ConclusionsThe 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.