Biochemical and genetic characteristics of 40 neonates with carnitine deficiency.
10.11817/j.issn.1672-7347.2020.190241
- Author:
Xiaoqiang ZHOU
1
;
Yanling TENG
2
;
Siyuan LIN-PENG
3
;
Zhuo LI
3
;
Lingqian WU
3
;
Desheng LIANG
4
Author Information
1. Center for Medical Genetics, School of Life Sciences, Central South University, Changsha 410078. 1926315667@qq.com.
2. Hunan Jiahui Genetic Specialist Hospital, Changsha 410078, China.
3. Center for Medical Genetics, School of Life Sciences, Central South University, Changsha 410078.
4. Center for Medical Genetics, School of Life Sciences, Central South University, Changsha 410078. Liangdesheng@sklmg.edu.cn.
- Publication Type:Journal Article
- Keywords:
SLC22A5;
free carnitine in blood;
gene mutation;
neonatal blood screening with tandem mass spectrometry;
primary carnitine deficiency
- MeSH:
Cardiomyopathies;
Carnitine/deficiency*;
Child;
Humans;
Hyperammonemia/genetics*;
Infant, Newborn;
Muscular Diseases/genetics*;
Mutation;
Solute Carrier Family 22 Member 5/genetics*
- From:
Journal of Central South University(Medical Sciences)
2020;45(10):1164-1171
- CountryChina
- Language:English
-
Abstract:
OBJECTIVES:Primary carnitine deficiency (PCD) is a rare fatty acid metabolism disorder that can cause neonatal death. This study aims to analyze carnitine levels and detect SLC22A5 gene in newborns with carnitine deficiency, to provide a basis for early diagnosis of PCD, and to explore the relationship between carnitine in blood and SLC22A5 genotype.
METHODS:A total of 40 neonates with low free carnitine (C0<10 μmol/L) in blood were the subjects of the study. SLC22A5 gene was detected by Sanger sequencing to analyze the value of carnitine, the results of gene test and their relationship.
RESULTS:A total of 15 variants of SLC22A5 gene were detected, including 11 pathogenic or likely pathogenic variants and 4 variants of uncertain significance. There were 5 new mutations: c.288delG (p.G96fsX33), c.744_745insTCG (p.M258_L259insS), c.752A>G (p.Y251C), c.495 C>A (p.R165E), and c.1298T>C (p.M433T). We found 14 PCD patients including 2 homozygous mutations and 12 heterozygous mutations, 14 with 1 mutation, and 12 with no mutation among 40 children. The C0 concentration of children with SLC22A5 gene homozygous or complex heterozygous mutations was (4.95±1.62) μmol/L in the initial screening, and (3.90±1.33) μmol/L in the second screening. The C0 concentration of children with no mutation was (7.04±2.05) μmol/L in the initial screening, and (8.02±2.87) μmol/L in the second screening. There were significant differences between children with homozygous or compound heterozygous mutations and with no mutation in C0 concentration of the initial and the second screening (both
CONCLUSIONS:There are 5 new mutations which enriched the mutation spectrum of SLC22A5 gene. C0<5 μmol/L is highly correlated with SLC22A5 gene homozygous or compound heterozygous mutations. Children with truncated mutation may have lower C0 concentration than that with untruncated mutation in the initial screening.
