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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.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.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.

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.

Background Glutaric acidemia type 1 (GA1) is a treatable disorder affecting cerebral organic acid metabolism caused by a defective glutaryl-CoA dehydrogenase (GCDH) gene. GA1 diagnosis reports following newborn screening (NBS) are scarce in the Chinese population. This study aimed to assess the acylcarnitine profiles and genetic characteristics of patients with GA1 identified through NBS. Results From January 2014 to September 2020, 517,484 newborns were screened by tandem mass spectrometry, 102 newborns with elevated glutarylcarnitine (C5DC) levels were called back. Thirteen patients were diagnosed with GA1, including 11 neonatal GA1 and two maternal GA1 patients. The incidence of GA1 in the Quanzhou region was estimated at 1 in 47,044 newborns. The initial NBS results showed that all but one of the patients had moderate to markedly increased C5DC levels. Notably, one neonatal patient with low free carnitine (C0) level suggest primary carnitine deficiency (PCD) but was ultimately diagnosed as GA1. Nine neonatal GA1 patients underwent urinary organic acid analyses: eight had elevated GA and 3HGA levels, and one was reported to be within the normal range. Ten distinct GCDH variants were identified. Eight were previously reported, and two were newly identified. In silico prediction tools and protein modeling analyses suggested that the newly identified variants were potentially pathogenic. The most common variant was c.1244-2 A>C, which had an allelic frequency of 54.55% (12/22), followed by c.1261G>A (p.Ala421Thr) at 9.09% (2/22). Conclusions Neonatal GA1 patients with increased C5DC levels can be identified through NBS. Maternal GA1 patients can also be detected using NBS due to the low C0 levels in their infants. Few neonatal GA1 patients may have atypical acylcarnitine profiles that are easy to miss during NBS; therefore, multigene panel testing should be performed in newborns with low C0 levels. This study indicates that the GCDH variant spectra were heterogeneous in this southern Chinese cohort.