Neonatal-onset primary mitochondrial disease caused by nuclear gene mutations: a report of 4 cases
10.3760/cma.j.issn.2096-2932.2024.01.008
- VernacularTitle:核基因变异致新生儿原发性线粒体疾病4例临床和基因分析
- Author:
Qingyang CUI
1
;
Yun SHANG
;
Yazhou SUN
;
Guimei SANG
;
Wen LI
;
Xiaori HE
;
Xiaoyun GONG
Author Information
1. 新乡医学院第一附属医院儿科，卫辉 453100
- Keywords:
Primary mitochondrial disease;
Nuclear gene;
Newborn;
Hyperlactatemia;
Cardiomyopathy
- From:Chinese Journal of Neonatology
2024;39(1):34-37
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To study the clinical manifestations and genetic characteristics of neonatal-onset primary mitochondrial disease (PMD) caused by nuclear gene mutations.Methods:From May 2020 to March 2022, the clinical data, genetic results and follow-up information of neonates with PMD admitted to the Department of Neonatology of our two hospitals were retrospectively analyzed.Results:A total of 4 patients were enrolled, all with hyperlactatemia and metabolic acidosis. In case 1, the fetal cranial MRI showed agenesis of corpus callosum. In case 2, echocardiography after birth indicated hypertrophic cardiomyopathy. Whole exome sequencing found the following mutations: EARS2 nuclear gene c.1294C>T and c.971G>T variants, COA6 nuclear gene c.411_412insAAAG variant, ACAD9 nuclear gene c.1278+1G>A and c.895A>T variants, FOXRED1 nuclear gene c.1054C>T and c.3dup variants. Mitochondrial second-generation sequencing and multiplex ligation-dependent probe amplification showed no abnormalities. Cases 1 and 3 died during the neonatal period. Case 2 died at 2-year-and-2-month of age. Case 4 was followed up to 1 year of age with developmental delay.Conclusions:The main phenotypes of neonatal-onset PMD caused by nuclear gene mutations are hyperlactatemia, refractory metabolic acidosis and cardiomyopathy, which have a poor prognosis. Proactive genetic tests are helpful for early diagnosis.
