Isovaleric acidemia due to compound heterozygous variants of IVD gene in a case.
10.3760/cma.j.cn511374-20200415-00271
- VernacularTitle:IVD基因复合杂合变异导致异戊酸血症一例
- Author:
Fengyu CHE
1
;
Ying YANG
;
Zhi WANG
;
Guoxia WANG
;
Haibin WU
;
Liyu ZHANG
;
Jiakai WEI
;
Yujuan ZHAO
;
Jiangang ZHAO
Author Information
1. Shaanxi Provincial Institute of Pediatrics, Xi'an Children's Hospital, Xi'an, Shaanxi 710002, China. 38821506@qq. com.
- Publication Type:Journal Article
- MeSH:
Amino Acid Metabolism, Inborn Errors/genetics*;
Child;
Female;
Heterozygote;
Humans;
Isovaleryl-CoA Dehydrogenase/genetics*;
Male;
Mutation
- From:
Chinese Journal of Medical Genetics
2021;38(2):150-153
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To analyze the clinical features, biochemical characteristics and molecular pathogenesis of a girl with isovaleric acidemia.
METHODS:Clinical features, blood spot amino acid profiles and urinary organic acid profiles of the patient were analyzed. Targeted capture, next generation sequencing and Sanger sequencing were carried out to detect potential variant of the IVD gene.
RESULTS:The patient presented with poor weight gain, poor feeding, lethargy, and a "sweaty feet" odor 10 days after birth. Biochemical test suggested hyperammonemia. Blood spot amino acid profiles displayed a dramatic increase in isovalerylcarnitine (C5: 3. 044, reference range 0.04 - 0.4 μmol/L). Organic acid analysis of her urine sample revealed a high level of isovaleric glycine (669. 53, reference range 0 - 0.5). The child was ultimately diagnosed with isovaleric acidemia, and was found to harbor a paternally derived heterozygous variant c.149G>A (p.R50H) and a maternally derived heterozygous variant c.1123G>A (p.G375S) of the IVD gene. Her elder brother was a heterozygous carrier of c.1123G>A (p.G375S) variant. The c.149G>A (p.R50H) was a known pathogenic variant, while the c.1123G>A (p.G375S) variant was previously unreported.
CONCLUSION:The pathogenesis of the patient was delineated from the perspective of genetics, which has provided a basis for clinical diagnosis, treatment as well as genetic counseling.
