Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.