Department of Paediatric Endocrinology, Royal Manchester Children's Hospital, Manchester M13 9WL, UK.
Eur J Endocrinol. 2011 May;164(5):733-40. doi: 10.1530/EJE-10-1136. Epub 2011 Mar 4.
In children with congenital hyperinsulinism (CHI), K(ATP) channel genes (ABCC8 and KCNJ11) can be screened rapidly for potential pathogenic mutations. We aimed to assess the contribution of rapid genetic testing to the clinical management of CHI.
Follow-up observational study at two CHI referral hospitals.
Clinical outcomes such as subtotal pancreatectomy, (18)F-Dopa positron emission tomography-computed tomography (PET-CT) scanning, stability on medical treatment and remission were assessed in a cohort of 101 children with CHI.
In total, 32 (32%) children had pathogenic mutations in K(ATP) channel genes (27 in ABCC8 and five in KCNJ11), of which 11 (34%) were novel. In those negative at initial screening, other mutations (GLUD1, GCK, and HNF4A) were identified in three children. Those with homozygous/compound heterozygous ABCC8/KCNJ11 mutations were more likely to require a subtotal pancreatectomy CHI (7/10, 70%). Those with paternal heterozygous mutations were investigated with (18)F-Dopa PET-CT scanning and 7/13 (54%) had a focal lesionectomy, whereas four (31%) required subtotal pancreatectomy for diffuse CHI. Those with maternal heterozygous mutations were most likely to achieve remission (5/5, 100%). In 66 with no identified mutation, 43 (65%) achieved remission, 22 (33%) were stable on medical treatment and only one child required a subtotal pancreatectomy.
Rapid genetic analysis is important in the management pathway of CHI; it provides aetiological confirmation of the diagnosis, indicates the likely need for a subtotal pancreatectomy and identifies those who require (18)F-Dopa PET-CT scanning. In the absence of a mutation, reassurance of a favourable outcome can be given early in the course of CHI.
在患有先天性高胰岛素血症（CHI）的儿童中，可以快速筛选 K(ATP)通道基因（ABCC8 和 KCNJ11）以寻找潜在的致病突变。本研究旨在评估快速基因检测对 CHI 临床管理的贡献。
在两家 CHI 转诊医院进行的随访观察性研究。
评估了 101 例 CHI 患儿的临床结局，包括次全胰切除术、18F-Dopa 正电子发射断层扫描-计算机断层扫描（PET-CT）扫描、药物治疗稳定性和缓解情况。
总共 32 例（32%）儿童的 K(ATP)通道基因存在致病性突变（ABCC8 中有 27 例，KCNJ11 中有 5 例），其中 11 例（34%）为新突变。在初次筛查阴性的患儿中，有 3 例发现了其他突变（GLUD1、GCK 和 HNF4A）。那些 ABCC8/KCNJ11 纯合/复合杂合突变的患儿更有可能需要行次全胰切除术治疗 CHI（7/10，70%）。那些具有父系杂合突变的患儿进行了 18F-Dopa PET-CT 扫描，其中 7/13 例（54%）有局灶性病变切除术，而 4/13 例（31%）因弥漫性 CHI 而行次全胰切除术。那些具有母系杂合突变的患儿最有可能获得缓解（5/5，100%）。在未发现突变的 66 例患儿中，有 43 例（65%）获得缓解，22 例（33%）药物治疗稳定，仅有 1 例患儿需要行次全胰切除术。
快速基因分析在 CHI 的管理路径中非常重要；它为诊断提供了病因学确认，提示可能需要行次全胰切除术，并确定需要进行 18F-Dopa PET-CT 扫描的患儿。在没有突变的情况下，可在 CHI 病程早期就对患儿的良好预后提供保证。
