The global prevalence and genetic spectrum of primary carnitine deficiency

• Published in: BMC genetics Vol. 26; no. 1; pp. 44 - 10
• Main Authors: Sun, Liu, Yao, Ke, Wu, Hang-Jing
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 07.07.2025; BioMed Central; BMC
• Subjects: Analysis; Annotations; Cardiomyopathies - epidemiology; Cardiomyopathies - genetics; Carnitine; Carnitine - deficiency; Carnitine - genetics; Carrier frequency; Case reports; Datasets; Dosage and administration; Fatty acids; Gene Frequency; Genetic aspects; Genome aggregation database (gnomAD); Genomes; Genomics; Health aspects; Hereditary diseases; Humans; Hyperammonemia - epidemiology; Hyperammonemia - ethnology; Hyperammonemia - genetics; Infants (Newborn); Levocarnitine; Medical screening; Muscular Diseases - epidemiology; Muscular Diseases - genetics; Organic cation/Carnitine transporter 2 (OCTN2); Pathogenicity; Prevalence; Prevalence studies (Epidemiology); Primary carnitine deficiency (PCD); Proteins; Rare diseases; Solute carrier family 22 member 5 (SLC22A5); Solute Carrier Family 22 Member 5 - genetics; China; Primary carnitine deficiency (PCD); Rare diseases; Carrier frequency; Genetic prevalence; Organic cation/Carnitine transporter 2 (OCTN2); Genome aggregation database (gnomAD); Solute carrier family 22 member 5 (SLC22A5)
• ISSN: 2730-6844; 2730-6844; 1471-2156
• DOI: 10.1186/s12863-025-01336-z

Primary carnitine deficiency (PCD) is an autosomal recessive rare disorder of carnitine cycle and carnitine transport caused by pathogenic variants 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. 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 variants of the SLC22A5 gene in 807,162 individuals was examined to estimate the global prevalence of PCD in nine ethnicities: African/African American (afr), Admixed American (amr), East Asian (eas), Non-Finnish European (nfe), South Asian (sas), Ashkenazi Jewish (asj), Middle Eastern (mid), Finnish (fin) and Remaining individuals (rmi). The global and population-specific carrier frequency and genetic prevalence of PCD were calculated using the Hardy-Weinberg equation. Total of 213 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 10.6 per thousand (1/95) and 28.2 per million (1/35427), respectively. The prevalence of PCD is estimated to be 1/35,000 globally, with a range of between 1/450,000 and 1/20,000 depending on ethnicity.