Birth weight and diazoxide unresponsiveness strongly predict the likelihood of congenital hyperinsulinism due to a mutation in ABCC8 or KCNJ11
Hewat, TI; Yau, D; Jerome, JCS; et al.Laver, TW; Houghton, JAL; Shields, BM; Flanagan, SE; Patel, KA
Date: 1 October 2021
Article
Journal
European Journal of Endocrinology
Publisher
European Society of Endocrinology / Bioscientifica
Publisher DOI
Abstract
Objective
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 KATPhyperinsulinism at diagnosis.
Design
We ...
Objective
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 KATPhyperinsulinism at diagnosis.
Design
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.
Methods
We compared the clinical features of KATP-hyperinsulinism and unknown hyperinsulinism cases. We
performed logistic regression and ROC analysis to identify the features that predict KATPhyperinsulinism.
Results
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). 86% born
large for gestation and 78% born appropriate for gestation 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 KATPhyperinsulinism.
Conclusions
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 for KATP channel genes.
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