Phenotypic and molecular features of Thai patients with primary carnitine deficiency
Issued Date
2023-01-01
Resource Type
eISSN
1442200X
Scopus ID
2-s2.0-85146484692
Pubmed ID
36321377
Journal Title
Pediatrics international : official journal of the Japan Pediatric Society
Volume
65
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Pediatrics international : official journal of the Japan Pediatric Society Vol.65 No.1 (2023) , e15404
Suggested Citation
Liammongkolkul S., Boonyawat B., Vijarnsorn C., Tim-Aroon T., Wasant P., Vatanavicharn N. Phenotypic and molecular features of Thai patients with primary carnitine deficiency. Pediatrics international : official journal of the Japan Pediatric Society Vol.65 No.1 (2023) , e15404. doi:10.1111/ped.15404 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/82597
Title
Phenotypic and molecular features of Thai patients with primary carnitine deficiency
Author's Affiliation
Other Contributor(s)
Abstract
BACKGROUND: Primary carnitine deficiency (PCD) is screened by expanded newborn screening (NBS) using tandem mass spectrometry (MS/MS) that can detect both affected neonates and mothers. This study aimed to delineate the clinical, biochemical, and molecular findings of Thai PCD patients. METHODS: Expanded NBS using MS/MS was implemented in Bangkok and 146,757 neonates were screened between 2014 and 2018. PCD was screened by low free carnitine (C0) levels in dried blood spots. Plasma C0 levels and C0 clearance values were measured in neonates and their mothers with positive screening results. Clinically diagnosed cases were described. The coding regions and intron-exon boundaries of the SLC22A5 gene were sequenced in all cases with low plasma C0 levels. RESULTS: There were 14 cases with confirmed PCD: two clinically diagnosed cases, and 12 cases identified through NBS including five newborns, six mothers, and one older sibling. Thus, the incidence of PCD in neonates was 1:29,351. All affected neonates and mothers were asymptomatic except one mother with dilated cardiomyopathy. SLC22A5 gene sequencing identified biallelic causative variants in all cases, comprising 10 different variants of which four were novel. c.51C > G (p.Phe17Leu) and c.760C > T (p.Arg254Ter) were the most prevalent variants in this study. Cases with significant clinical features tended to have higher C0 clearance values. CONCLUSIONS: Primary carnitine deficiency is a common inherited metabolic disorder (IMD) in Thailand. Our findings broaden the spectrum of SLC22A5 variants. The future national NBS program will shed more light on PCD and other IMDs in Thailand.