Zailong Qin1, Qi Yang1, Shang Yi1, Limei Huang1, Yiping Shen1,2, Jingsi Luo1. 1. Genetic and Metabolic Central Laboratory, Guangxi Birth Defects Research and Prevention Institute, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China. 2. Department of Genetics, Harvard Medical School, Boston, MA, USA.
Abstract
BACKGROUND: Liver failure caused by TRMU is a rare hereditary disorder and clinically manifests into metabolic acidosis, hyperlactatemia, and hypoglycemia. Limited spectrum of TRMU pathogenic variants has been reported. METHODS: Whole-exome sequencing was employed for the diagnosis of a 5-day-old female who suffered from severe neonatal hyperlactatemia and hypoglycemia since birth. Sanger sequencing was performed to confirm the origin of the variants subsequently. Variants classification was followed to ACMG guideline. RESULTS: A compound heterozygosity of a frameshiftc.34_35dupTC (p.Gly13fs) and a missense c.244T>G (p.Phe82Val) in TRMU was detected, both variants are novel and pathogenic. Analysis of clinical and genetic information including patients reported previously indicated that there is no significant correlation between the genotype and the phenotype of TRMU-caused liver failure. CONCLUSION: To the best of our knowledge, this is the first case report of TRMU-caused liver failure in China. Whole-exome sequencing is effective for conclusive diagnosis of this disorder and beneficial for its clinical management.
BACKGROUND:Liver failure caused by TRMU is a rare hereditary disorder and clinically manifests into metabolic acidosis, hyperlactatemia, and hypoglycemia. Limited spectrum of TRMU pathogenic variants has been reported. METHODS: Whole-exome sequencing was employed for the diagnosis of a 5-day-old female who suffered from severe neonatal hyperlactatemia and hypoglycemia since birth. Sanger sequencing was performed to confirm the origin of the variants subsequently. Variants classification was followed to ACMG guideline. RESULTS: A compound heterozygosity of a frameshiftc.34_35dupTC (p.Gly13fs) and a missense c.244T>G (p.Phe82Val) in TRMU was detected, both variants are novel and pathogenic. Analysis of clinical and genetic information including patients reported previously indicated that there is no significant correlation between the genotype and the phenotype of TRMU-caused liver failure. CONCLUSION: To the best of our knowledge, this is the first case report of TRMU-caused liver failure in China. Whole-exome sequencing is effective for conclusive diagnosis of this disorder and beneficial for its clinical management.
Authors: G M Enns; M J Bennett; C L Hoppel; S I Goodman; K Weisiger; C Ohnstad; M Golabi; S Packman Journal: J Pediatr Date: 2000-02 Impact factor: 4.406
Authors: Giuseppe Indolfi; Maria Iascone; Giulia Remaschi; Maria A Donati; Claudia Nesti; Anna Rubegni; Laura Pezzoli; Anna M Buccoliero; Filippo M Santorelli; Massimo Resti Journal: J Pediatr Gastroenterol Nutr Date: 2017-09 Impact factor: 2.839