Biochemical and genetic characteristics of patients with primary carnitine deficiency identified through newborn screening

Abstract

Background Primary carnitine deficiency (PCD) is an autosomal recessive disorder of carnitine transportation that leads to impaired fatty acid oxidation. Large-scale studies on newborn screening (NBS) for PCD are limited. This study aimed to investigate the biochemical and genetic characteristics of patients with PCD detected through NBS. Results A total of 548 247 newborns were screened for PCD between January 2014 and June 2021; 1714 newborns with low free carnitine (C0) levels were called back and 49 patients were diagnosed with PCD. The latest incidence rate in Quanzhou, China, was estimated to be 1 in 11 189 newborns. NBS results showed that the 49 patients had varying degrees of decreased C0 levels, whereas seven patients exhibited normal C0 levels during the recall review. All patients harbored biallelic pathogenic variants of the SLC22A5 gene. Nineteen distinct SLC22A5 variants were detected in these 49 patients, and most of the detected variants were clustered in exons 1, 4, and 7. The top eight variants had an allele frequency of 86.73%. The most common variant was c.760C > T (p.R254*) with an allele frequency of 31.63%, followed by c.51C > G (p.F17L) (17.35%) and c.1400C > G (p.S467C) (16.33%). The C0 level of patients with the N/N genotype was significantly lower than that of the M/M group. The C0 levels of patients with genotypes of R254*/R254* and R254*/F17L were far lower than those of patients with the R254*/S467C genotype. Conclusions This study presented more than 500,000 NBS data with the latest incidence of 1:11 189 in the Quanzhou area. The SLC22A5 variant spectrum in the selected southern Chinese population has been updated. Patients with null variants were associated with low C0 levels. Combining NBS with genetic testing is critical to improve screening efficiency because patients with PCD may have normal C0 levels during NBS and recall review.

Phenotypic and molecular features of Thai patients with primary carnitine deficiency

“…The relationship between plasma C0 levels and the SLC22A5 genotypes in neonates with abnormal NBS has shown variable results among studies. 24,28,31 In our study, three patients with higher C0 clearance values (≥150%) developed either hepatic or cardiac manifestations. In contrast, these manifestations were not found in maternal PCD cases with lower C0 clearance values (<100%).…”

“…This suggests that other genetic or environmental factors may contribute to the phenotypes. The relationship between plasma C0 levels and the SLC22A5 genotypes in neonates with abnormal NBS has shown variable results among studies 24,28,31 . In our study, three patients with higher C0 clearance values (≥150%) developed either hepatic or cardiac manifestations.…”

Newborn Screening of Primary Carnitine Deficiency: An Overview of Worldwide Practices and Pitfalls to Define an Algorithm before Expansion of Newborn Screening in France

“…From the above-mentioned studies, we gathered individual molecular data that were available [ 58 , 64 , 72 , 73 , 78 , 80 , 83 , 86 , 89 , 92 , 96 , 98 , 101 , 103 , 104 , 107 , 110 ]. Genotype data were described for 175 newborns and C 0 levels on screening were mentioned for 132 of the newborns.…”

Correction to: Biochemical and genetic characteristics of patients with primary carnitine deficiency identified through newborn screening

“…Following the publication of the original article [ 1 ] the authors reported an error in Table 1 (page 3 of the PDF).…”

“…Author details 1 Center of Neonatal Disease Screening, Quanzhou Maternity and Children's Hospital, 700 Fengze Street, Quanzhou 362000, Fujian Province, China. 2 Administrative Office, Quanzhou Maternity and Children's Hospital, 700 Fengze Street, Quanzhou 362000, Fujian Province, China.…”