Congenital hyperinsulinism: current status and future perspectives

Abstract

The diagnosis and treatment of congenital hyperinsulinism (CHI) have made a remarkable progress over the past 20 years and, currently, it is relatively rare to see patients who are left with severe psychomotor delay. The improvement was made possible by the recent developments in the understanding of the molecular and pathological basis of CHI. Known etiologies include inactivating mutations of the KATP channel genes (ABCC8 and KCNJ11) and HNF4A, HNF1A, HADH, and UCP2 or activating mutations of GLUD1, GCK, and SLC16A1. The understanding of the focal form of KATP channel CHI and its detection by 18F-fluoro-L-DOPA positron emission tomography have revolutionized the management of CHI, and many patients can be cured without postoperative diabetes mellitus. The incidence of the focal form appears to be higher in Asian countries; therefore, the establishment of treatment systems is even more important in this population. In addition to diazoxide or long-term subcutaneous infusion of octreotide or glucagon, long-acting octreotide or lanreotide have also been used successfully until spontaneous remission. Because of these medications, near-total pancreatectomy is less often performed even for the diazoxide-unresponsive diffuse form of CHI. Other promising medications include pasireotide, small-molecule correctors such as sulfonylurea or carbamazepine, GLP1 receptor antagonists, or mammalian target of rapamycin inhibitors. Unsolved questions in this field include the identification of the remaining genes responsible for CHI, the mechanisms leading to transient CHI, and the mechanisms responsible for the spontaneous remission of CHI. This article reviews recent developments and hypothesis regarding these questions.

Treatment and Follow-up in a Case with Diazoxide Treatment-Resistant Hyperinsulinemic Hypoglycaemia

“…Diffüz β hücre hiperplazisinde genetik yapı heterojendir; otozomal resesif (ABCC8, KCNJ11) veya otozomal dominant (ABCC8/KCNJ11, GCK, GLUD1, SLC16A1, HNF4A, HADH) gen mutasyonları olabilir (1,2). Olguların yarısına genetik olarak tanı konamazken, bilinen en sık neden ABCC8/KCNJ11 genlerinde otozomal resesif inaktive edici mutasyondur (2,4). ABCC8/KCNJ11 mutasyonları haricindeki mutasyonlarda çoğunlukla diazoksite yanıt vardır (1,2).…”

“…Oktreotidin diffüz hastalığın medikal tedavisinde uzun dönemde de, enteral beslenme ile uygulanabilir. Diazoksit yanıtsız potasyum kanal defektlerinde 2-5 yaşlarında spontan remisyona uğrayana kadar oktreotidin uzun dönemde başarılı bir şekilde kullanıldığı bildirilmiştir (4). Nifedipin bir kalsiyum kanal antagonistidir ve şimdiye kadar nifedipine yanıtlı sadece birkaç olgu bildirilmiştir (2).…”

“…Yenidoğan ve süt çocuklarında ısrarlı hipogliseminin en sık sebebidir (2)(3)(4). Sporadik ve genetik nedenli HH nadir görülürken (insidansı 1/40000) akraba evliliği sık görülen yerlerde insidans 1/2500'e kadar çıkabilir (2).…”

Hiperinsulinismo congénito del recién nacido: A propósito de un caso clínico

“…Laidlaw described it in 1938 and called it 'Nesidioblastosis' 5 . It is currently described as a heterogeneous condition in clinical presentation, genetics, histology and response to treatment 3 . HC is characterized by inadequate and unregulated insulin production when blood glucose levels are low 6 .…”

“…Congenital hyperinsulinism (HC) is the main cause of persistent and recurrent hypoglycemia in the first year of life [1][2][3] . Its incidence ranges from 1/27,000 to 1/50,000 in newborns 4 .…”