Newborn screening for fatty acid oxidation disorders in a southern Chinese population

Yiming Lin; Chunmei Lin; Bangbang Lin; Zhenzhu Zheng; Weihua Lin; Yanru Chen; Dongmei Chen; Weilin Peng

doi:10.1016/j.heliyon.2023.e23671

Newborn screening for fatty acid oxidation disorders in a southern Chinese population

Heliyon. 2023 Dec 13;10(1):e23671. doi: 10.1016/j.heliyon.2023.e23671. eCollection 2024 Jan 15.

Authors

Yiming Lin¹, Chunmei Lin¹, Bangbang Lin², Zhenzhu Zheng¹, Weihua Lin³, Yanru Chen³, Dongmei Chen⁴, Weilin Peng¹

Affiliations

¹ Department of Clinical Laboratory, Quanzhou Maternity and Children's Hospital, 700 Fengze Street, Quanzhou, Fujian Province, 362000, China.
² Administrative office, Quanzhou Maternity and Children's Hospital, 700 Fengze Street, Quanzhou, Fujian Province, 362000, China.
³ Center of Neonatal Disease Screening, Quanzhou Maternity and Children's Hospital, 700 Fengze Street, Quanzhou, Fujian Province, 362000, China.
⁴ Department of Neonatology, Quanzhou Maternity and Children's Hospital, 700 Fengze Street, Quanzhou, Fujian Province, 362000, China.

Abstract

Background and aims: Fatty acid oxidation disorders (FAODs) are a group of autosomal recessive metabolic diseases included in many newborn screening (NBS) programs, but the incidence and disease spectrum vary widely between ethnic groups. We aimed to elucidate the incidence, disease spectrum, and genetic features of FAODs in a southern Chinese population.

Materials and methods: The FAODs screening results of 643,606 newborns from 2014 to 2022 were analyzed.

Results: Ninety-two patients were eventually diagnosed with FAODs, of which 61 were PCD, 20 were MADD, 5 were SCADD, 4 were VLCADD, and 2 were CPT-IAD. The overall incidence of FAODs was 1:6996 (95 % CI: 1:5814-1:8772) newborns. All PCD patients had low C0 levels during NBS, while nine patients (14.8 %) had normal C0 levels during the recall review. All but one MADD patients had elevated C8, C10, and C12 levels during NBS, while eight patients (40 %) had normal acylcarnitine levels during the recall review. The most frequent SLC22A5 variant was c.760C > T (p.R254*) with an allele frequency of 29.51 %, followed by c.51C > G (p.F17L) (17.21 %) and c.1400C > G (p.S467C) (16.39 %). The most frequent ETFDH variant was c.250G > A (p.A84T) with an allelic frequency of 47.5 %, followed by c.524G > A (R175H) (12.5 %), c.998A > G (p.Y333C) (12.5 %), and c.1657T > C (p.Y553H) (7.5 %).

Conclusion: The prevalence, disease spectrum, and genetic characteristics of FAODs in a southern Chinese population were clarified. PCD was the most common FAOD, followed by MADD. Hotspot variants were found in SLC22A5 and ETFDH genes, while the remaining FAODs showed great molecular heterogeneity. Incorporating second-tier genetic screening is critical for FAODs.

Keywords: Fatty acid oxidation disorders; Multiple acyl-CoA dehydrogenase deficiency; Newborn screening; Primary carnitine deficiency; Tandem mass spectrometry.