Department of Neonatology, National Children's Medical Center, Children's Hospital of Fudan University, Shanghai, China.
Clinical Genetic Center, National Children's Medical Center, Children's Hospital of Fudan University, Shanghai, China.
Neonatology. 2022;119(1):103-110. doi: 10.1159/000519634. Epub 2021 Nov 19.
The genetic characteristics in neonates admitted to the NICU with recurrent hypernatremia remained unknown. We aimed to implement early genetic sequencing to identify possible genetic etiologies, optimize the treatment, and improve the outcome.
We prospectively performed exome sequencing or targeted panel sequencing on neonates diagnosed with recurrent hypernatremia (plasma sodium ≥150 mEq/L, ≥2 episodes) from January 1, 2016, to June 30, 2020.
Among 22,375 neonates admitted to the NICU, approximately 0.33% (73/22,375) developed hypernatremia. The incidence of hypernatremia >14 days and ≤14 days was 0.03% and 0.3%, respectively. Among 38 neonates who had ≥2 hypernatremia episodes, parents of 28 patients consented for sequencing. Genetic diagnosis was achieved in 25% neonates (7/28). Precision medicine treatment was performed in 85.7% (6/7) of the patients, including hydrochlorothiazide and indomethacin for 57.1% (4/7) with arginine vasopressin receptor 2 (AVPR2) deficiency-associated congenital nephrogenic diabetes insipidus; a special diet of fructose formula for 1 patient with solute carrier family 5 member 1 deficiency-associated congenital glucose-galactose malabsorption (1/7, 14.3%); and kallikrein-inhibiting ointment for 1 patient with serine protease inhibitor of Kazal-type 5 deficiency-associated Netherton syndrome (1/7, 14.3%). Only hypernatremia onset age (adjusted odds ratio 1.32 [1.01-1.72], p = 0.040) independently predicted the underlying genetic etiology. The risk of a genetic etiology of hypernatremia was 9.0 times higher for neonates with a hypernatremia onset age ≥17.5 days (95% confidence interval, 1.1-73.2; p = 0.038).
Single-gene disorders are common in neonates with recurrent hypernatremia, and >50% of cases are caused by AVPR2 deficiency-associated congenital nephrogenic diabetes insipidus. Early genetic testing can aid the diagnosis of unexplained recurrent neonatal hypernatremia and improve therapy and outcome.
新生儿重症监护病房（NICU）中反复高钠血症患儿的遗传特征尚不清楚。我们旨在通过早期基因测序来确定可能的遗传病因，优化治疗方法并改善预后。
我们前瞻性地对 2016 年 1 月 1 日至 2020 年 6 月 30 日期间在 NICU 中被诊断为反复高钠血症（血浆钠≥150mEq/L，≥2 次发作）的新生儿进行了外显子组测序或靶向panel 测序。
在 22375 名入住 NICU 的新生儿中，约有 0.33%（73/22375）发生高钠血症。高钠血症持续时间>14 天和≤14 天的发生率分别为 0.03%和 0.3%。在 38 名有≥2 次高钠血症发作的患儿中，有 28 名患儿的父母同意进行测序。在 28%的患儿中（7/28）获得了遗传诊断。对 85.7%（6/7）的患儿进行了精准医学治疗，其中 57.1%（4/7）为精氨酸加压素受体 2（AVPR2）缺陷相关先天性肾性尿崩症，给予氢氯噻嗪和吲哚美辛；1 例溶质载体家族 5 成员 1 缺陷相关先天性葡萄糖-半乳糖吸收不良的患儿给予果糖配方特殊饮食（1/7，14.3%）；1 例丝氨酸蛋白酶抑制剂 Kazal 型 5 缺陷相关 Netherton 综合征的患儿给予 Kallikrein-inhibiting 软膏（1/7，14.3%）。只有高钠血症发作年龄（调整后的优势比 1.32[1.01-1.72]，p=0.040）可独立预测潜在的遗传病因。高钠血症发作年龄≥17.5 天的新生儿发生高钠血症的遗传病因风险高 9.0 倍（95%置信区间，1.1-73.2；p=0.038）。
单基因疾病在反复高钠血症的新生儿中很常见，超过 50%的病例是由 AVPR2 缺陷相关先天性肾性尿崩症引起的。早期基因检测有助于诊断不明原因的新生儿反复高钠血症，并改善治疗效果和预后。
