Liang Wenyi, Xu Fanshu, Lu Yulan, Chen Huiyao, Chen Xiang, Xiao Hui, Hu Liyuan
Department of Neonatology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
National Health Commission (NHC) Key Laboratory of Neonatal Diseases, Fudan University, Children's Hospital of Fudan University, Shanghai, China.
Transl Pediatr. 2025 Feb 28;14(2):240-251. doi: 10.21037/tp-24-485. Epub 2025 Feb 25.
The genetic etiology and clinical characteristics of neonates with hyperkalemia remain unknown. We aimed to implement early gene sequencing to identify genetic causes, optimize treatment and improve outcomes in this population.
We retrospectively studied the clinical characteristics and genetic etiology of neonates with hyperkalemia who underwent exome sequencing or targeted panel sequencing from January 1, 2016, to December 31, 2023, at the Department of Neonatology, Children's Hospital of Fudan University.
Among 3,757 neonates with hyperkalemia, approximately 14.08% underwent sequencing. The average gestational age was 34.82±3.94 weeks, and the average birth weight was 2,375.22±864.09 grams. Males accounted for 56.0% of the cohort. The risk factors for hereditary hyperkalemia included dry skin, pigmentation and pseudohermaphroditism. Of these factors, only pigmentation independently predicted the genetic etiology of hyperkalemia; the presence of pigmentation increased the risk of hyperkalemia by 29.586 times [odds ratio (OR) 29.586, confidence interval (CI): 4.927-177.649, P<0.001]. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, we found that 7.56% hyperkalemia neonates had a genetic diagnosis; 28 genes were identified, including 18 genes not previously reported. Among genetic diseases, congenital adrenal hyperplasia (CAH) had the highest incidence (1.7%). For neonates with mineralocorticoid deficiency, early treatment with hydrocortisone reduced adverse outcomes to some extent. Gene Ontology (GO) analysis indicated that these genes were enriched primarily in nephron development.
The genetic etiology of neonatal hyperkalemia is complex. When clinical manifestations involve risk factors, it is advisable to conduct hormone testing and provide symptomatic treatment. Early genetic testing can aid in the diagnosis of hyperkalemia and improve the treatment of neonates with atypical clinical manifestations.
高钾血症新生儿的遗传病因和临床特征尚不清楚。我们旨在通过早期基因测序来确定遗传病因，优化治疗方案并改善该人群的治疗效果。
我们回顾性研究了2016年1月1日至2023年12月31日在复旦大学附属儿科医院新生儿科接受外显子组测序或靶向基因panel测序的高钾血症新生儿的临床特征和遗传病因。
在3757例高钾血症新生儿中，约14.08%接受了测序。平均胎龄为34.82±3.94周，平均出生体重为2375.22±864.09克。男性占该队列的56.0%。遗传性高钾血症的危险因素包括皮肤干燥、色素沉着和假两性畸形。在这些因素中，只有色素沉着独立预测了高钾血症的遗传病因；色素沉着的存在使高钾血症风险增加了29.586倍[比值比（OR）29.586，置信区间（CI）：4.927 - 177.649，P<0.001]。根据美国医学遗传学与基因组学学会（ACMG）指南，我们发现7.56%的高钾血症新生儿有遗传诊断；共鉴定出28个基因，其中包括18个以前未报道的基因。在遗传疾病中，先天性肾上腺皮质增生症（CAH）发病率最高（1.7%）。对于盐皮质激素缺乏的新生儿，早期使用氢化可的松治疗在一定程度上降低了不良结局。基因本体论（GO）分析表明，这些基因主要富集于肾单位发育。
新生儿高钾血症的遗传病因复杂。当临床表现涉及危险因素时，建议进行激素检测并给予对症治疗。早期基因检测有助于高钾血症的诊断，并改善非典型临床表现新生儿的治疗。
