Phenotypic and molecular features of Thai patients with primary carnitine deficiency

Abstract

BackgroundPrimary 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.MethodsExpanded 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.ResultsThere 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.ConclusionsPrimary 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.

Screening primary carnitine deficiency in 10 million Chinese newborns: a systematic review and meta-analysis

“…Globally, the Faroe Islands exhibit the highest incidence of PCD, with a prevalence of up to 1:297 [ 7 ]. This ratio varies across different regions, estimated at 1:50,000 in the United States [ 9 ], 1:25,000 in Egypt [ 24 ], 1:30,000 in Thailand [ 10 ], and 1:40,000 in Japan [ 25 ]. It is worth noting that the estimated prevalence of PCD is 1:17,641 in China based on the carrier frequency of SLC22A5 pathogenic or likely pathogenic (P/LP) variants from the Chinese Newborn Genome Project [ 26 ].…”

“…Several ethnic-specific variant spectra of SLC22A5 have been identified in different populations. For example, c.95A > G (p.N32S) is predominant in the Faroe Islands [ 7 ], c.136C > T (p.P46S) in the United States [ 33 ], c.51C > G (p.Phe17Leu) in Thailand [ 10 ], c.760C > T (p.R254X) and c.454G > C (p.G152R) in Turkey [ 34 ], and c.1400C > G (p.S467C) in Japan [ 25 ].…”

“…The estimated incidence of PCD varies widely across countries due to region and race, ranging from 1:120,000 to 1:300 newborns [ 7 – 10 ]. Additionally, significant differences in the incidence of PCD have been reported among different regions within China, with rates ranging from 1:100,000 to 1:3000 newborns [ 11 – 15 ].…”