Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK.
Department of Paediatric Endocrinology, Royal Manchester Children's Hospital, Manchester, UK.
Eur J Endocrinol. 2021 Oct 30;185(6):813-818. doi: 10.1530/EJE-21-0476.
Mutations in the KATP channel genes, ABCC8 and KCNJ11, are the most common cause of congenital hyperinsulinism. The diagnosis of KATP-hyperinsulinism is important for the clinical management of the condition. We aimed to determine the clinical features that help to identify KATP-hyperinsulinism at diagnosis.
We studied 761 individuals with KATP-hyperinsulinism and 862 probands with hyperinsulinism of unknown aetiology diagnosed before 6 months of age. All were referred as part of routine clinical care.
We compared the clinical features of KATP-hyperinsulinism and unknown hyperinsulinism cases. We performed logistic regression and receiver operator characteristic (ROC) analysis to identify the features that predict KATP-hyperinsulinism.
Higher birth weight, diazoxide unresponsiveness and diagnosis in the first week of life were independently associated with KATP-hyperinsulinism (adjusted odds ratio: 4.5 (95% CI: 3.4-5.9), 0.09 (0.06-0.13) and 3.3 (2.0-5.0) respectively). Birth weight and diazoxide unresponsiveness were additive and highly discriminatory for identifying KATP-hyperinsulinism (ROC area under the curve for birth weight 0.80, diazoxide responsiveness 0.77, and together 0.88, 95% CI: 0.85-0.90). In this study, 86% born large for gestation and 78% born appropriate for gestation and who did not respond to diazoxide treatment had KATP-hyperinsulinism. In contrast, of those individuals born small for gestation, none who were diazoxide responsive and only 4% of those who were diazoxide unresponsive had KATP-hyperinsulinism.
Individuals with hyperinsulinism born appropriate or large for gestation and unresponsive to diazoxide treatment are most likely to have an ABCC8 or KCNJ11 mutation. These patients should be prioritised for genetic testing of KATP channel genes.
ABCC8 和 KCNJ11 基因中的突变是先天性高胰岛素血症的最常见原因。KATP 高胰岛素血症的诊断对于该疾病的临床管理非常重要。我们旨在确定有助于在诊断时识别 KATP 高胰岛素血症的临床特征。
我们研究了 761 名 KATP 高胰岛素血症患者和 862 名在 6 个月龄前诊断为病因不明的高胰岛素血症的先证者。所有患者均因常规临床护理而就诊。
我们比较了 KATP 高胰岛素血症和病因不明的高胰岛素血症病例的临床特征。我们进行了逻辑回归和接收器操作特征 (ROC) 分析，以确定预测 KATP 高胰岛素血症的特征。
较高的出生体重、二氮嗪无反应和在生命的第一周内诊断与 KATP 高胰岛素血症独立相关（调整后的优势比：4.5（95%CI：3.4-5.9）、0.09（0.06-0.13）和 3.3（2.0-5.0））。出生体重和二氮嗪无反应是识别 KATP 高胰岛素血症的重要且高度区分性特征（出生体重的 ROC 曲线下面积为 0.80，二氮嗪反应性为 0.77，两者联合为 0.88，95%CI：0.85-0.90）。在这项研究中，86%的胎龄大于胎龄出生和 78%的胎龄正常出生且对二氮嗪无反应的患者患有 KATP 高胰岛素血症。相比之下，胎龄小于胎龄出生的患者中，无二氮嗪反应性患者中没有 KATP 高胰岛素血症，仅有 4%的二氮嗪无反应患者患有 KATP 高胰岛素血症。
胎龄大于胎龄或正常且对二氮嗪无反应的高胰岛素血症患者最有可能存在 ABCC8 或 KCNJ11 突变。这些患者应优先进行 KATP 通道基因突变检测。
