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Background and Aims: Primary carnitine deficiency (PCD) is an autosomal recessive disease caused by functional defects in the carnitine transporter OCTN2 due to mutations in SLC22A5. Here, we aimed to understand the incidence, clinical, biochemical, and molecular features of PCD in Quanzhou, China., Materials and Methods: Newborn screening (NBS) was performed through tandem mass spectrometry (MS/MS) to detect genetic metabolic diseases. Next-generation sequencing was used to detect SLC22A5 mutations in patients with suspected PCD., Results: From 364,545 newborns screened, 36 were diagnosed with PCD, in addition to five mothers. The incidence of PCD in children in the Quanzhou area was 1:10126. Eighteen SLC22A5 variants were found, with five novel ones. The most prevalent variant in neonatal and maternal patients was c.760C > T (p.R254*). Twenty-five neonatal patients received L-carnitine supplementation; however, one patient discontinued treatment and sudden death occurred. One sibling presented repeated fatigue, hypoglycemia, and coma, but the symptoms disappeared after treatment. Two mothers with PCD claimed to feel weak and easily fatigued., Conclusion: The incidence of PCD is relatively high in the Quanzhou area. Five novel variants were found, broadening the mutation spectrum of SLC22A5. NBS is effective in identifying PCD, and sudden death may be prevented with timely treatment., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Isovaleric acidemia (IVA) is a rare autosomal recessive disorder of leucine metabolism caused by a defective isovaleryl-CoA dehydrogenase (IVD) gene. Reports of IVA diagnoses following newborn screening (NBS) in the Chinese population are few., Methods: We investigated the biochemical, clinical, and molecular profiles of 5 patients with IVA in China. The estimated incidence of IVA in Quanzhou, China is 1 in 1:84,469., Results: Initial NBS revealed mild to markedly increased isovalerylcarnitine (C5) concentrations in all 5 patients, and differential diagnosis revealed increased urinary isovaleryglycine concentrations in 2 patients. One patient presented with acute neonatal symptoms, whereas the other 4 remained asymptomatic. Eight distinct IVD gene variants were identified. The most common variant was c.1208A > G (p.Y403C), with an allele frequency of 30%. Five variants were previously unreported, namely, c.499A > G (p.M167V), c.640A > G (p.T214A), c.740G > A (p.G247E), c.832G > C (p.V278L), and c.1195G > C (p.D399H). Different in silico prediction analyses suggested that these previously unreported missense variants are pathogenic. Protein modelling analyses also showed that these missense variants may cause structural damage and dysfunction in IVD., Conclusions: Patients with IVA may have C5 concentrations approaching the cut-off values, highlighting the need for stringent recall criteria and second-tier tests to improve screening performance., (Copyright © 2020 Elsevier B.V. All rights reserved.)