Gong Chunxiu, Huang Shuyue, Su Chang, Qi Zhan, Liu Fang, Wu Di, Cao Bingyan, Gu Yi, Li Wenjin, Liang Xuejun, Liu Min
Department of Pediatric Endocrinology and Genetic Metabolism, Beijing Children's Hospital Affiliated with Capital Medical University, Beijing, China.
Department of Pediatrics, Beijing Children's Hospital Affiliated with Capital Medical University, Beijing, China.
Pediatr Diabetes. 2016 May;17(3):227-34. doi: 10.1111/pedi.12254. Epub 2015 Feb 2.
The aim of this study is to investigate the clinical features, therapeutic outcomes, and genetic mutations of congenital hyperinsulinism (CHI) in Chinese patients.
The clinical features and therapeutic outcomes of 95 CHI cases were recorded, and genetic analyses were conducted to identify mutations in ABCC8 and KCNJ11 in 55 cases. Direct sequencing was carried out in 25 of the cases with ABCC8 and KCNJ11 mutations. Additionally, 16 samples with no mutations and the remaining 30 samples were sequenced using Ion Torrent platform.
Clinical misdiagnosis occurred in 36/95 (38%) of the cases. Most (82/95; 84%) of the patients were given diazoxide therapy combined with age-dependent frequent feeding, which was effective in 54/95 (66%) cases. The side effects of diazoxide included sodium and water retention, gastrointestinal reactions, polytrichia, and thrombocytopenia. Five patients were treated with octreotide for 1-4 months, of which 80% (4/5) showed a positive response. Non-surgical therapy was effective in 71/95 (75%) cases. Of the four children who received subtotal pancreatectomy, only one had a good outcome. The remission rate of hypoglycemia was 59% for children over 2-yr-old. The CHI-related gene mutation rate was 38% for potassium channel-related genes. Early onset of CHI and a lower diazoxide response rate were associated with potassium-ATP channel gene mutations.
Age-dependent frequent feeding is an acceptable therapy for CHI. Non-surgical therapy may be highly effective, in part, due to the low rate of potassium channel gene mutations. Surgical outcomes are unreliable without 18F-fluoro-L-DOPA positron emission tomography. Therefore, we do not recommend operation without definitive identification of the pathologic type.
本研究旨在调查中国先天性高胰岛素血症（CHI）患者的临床特征、治疗效果及基因突变情况。
记录95例CHI患者的临床特征及治疗效果，并对其中55例进行基因分析以鉴定ABCC8和KCNJ11基因的突变情况。对25例ABCC8和KCNJ11基因突变的患者进行直接测序。此外，对16例无突变样本及其余30例样本采用Ion Torrent平台进行测序。
95例患者中有36例（38%）发生临床误诊。大多数患者（82/95；84%）接受了二氮嗪治疗并结合年龄相关的频繁喂养，其中54例（66%）有效。二氮嗪的副作用包括钠水潴留、胃肠道反应、多毛症和血小板减少。5例患者接受奥曲肽治疗1 - 4个月，其中80%（4/5）有阳性反应。非手术治疗在71/95（75%）的病例中有效。接受胰腺次全切除术的4例患儿中，仅1例效果良好。2岁以上儿童低血糖缓解率为59%。钾通道相关基因的CHI相关基因突变率为38%。CHI的早发和较低的二氮嗪反应率与钾-ATP通道基因突变有关。
年龄相关的频繁喂养是CHI可接受的治疗方法。非手术治疗可能非常有效，部分原因是钾通道基因突变率较低。在未进行18F-氟-L-多巴正电子发射断层扫描的情况下，手术效果不可靠。因此，在未明确病理类型之前，我们不建议进行手术。
