Novel Compound Heterozygous Variants of the ABCC8 Gene Warrant Identification of Pancreatic Histology in Infant with Diazoxide-unresponsive Congenital Hyperinsulinism.

Rana Al Balwi,Raed Al Nefily,Omar Al Ghamdi,Dalal Bubshait

doi:10.3390/children8100836

Rana Al Balwi, Raed Al Nefily + Show 2 more

Open Access

https://doi.org/10.3390/children8100836

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Abstract

Congenital hyperinsulinism (CHI) is characterized by dysregulated insulin secretion, resulting in severe hypoglycemia. Mutations in the ABCC8 and KCNJ11 genes encoding KATP channels in beta cells of the pancreas are common among patients with CHI. Autosomal recessive CHI with diffuse involvement is the most common type of CHI among Saudi patients. It is relatively common for patients with autosomal recessive CHI to be medically unresponsive and undergo pancreatectomy. In this case report, we describe novel compound heterozygous variants in the ABCC8 gene in a Saudi infant that caused diazoxide-unresponsive CHI. The variants included a monoallelic paternally inherited variant that has been previously reported to cause a focal form of CHI and a maternally inherited variant of unknown significance (VUS). The severity of CHI in this patient was mild over the one-year follow-up period, with a near-optimal glycemic response on a low dose of octreotide. We suspected an atypical subtype of histological involvement in the patient. In this report, we highlight the phenotypic spectrum of novel compound heterozygous variants in a patient with CHI and consider that the report can help establish the pathogenicity of the VUS.

Highlights

Congenital hyperinsulinism (CHI) is one of the most common causes of recurrent hypoglycemia in early infancy
Biallelic ABCC8 mutations result in the diffuse form of CHI, whereas monoallelic mutations can result in either asymptomatic conditions or focal forms of CHI
Diazoxide is usually ineffective in treating patients with CHI due to biallelic recessive mutations in the genes encoding key genes encoding the potassium ATP channel (KATP) channel or presence of monoallelic focal form of disease [13,14]

Summary

Introduction

Congenital hyperinsulinism (CHI) is one of the most common causes of recurrent hypoglycemia in early infancy. The diffuse form of CHI is the most common type of mutation inheritance in the Saudi population [11] and it is not uncommon for patients with homozygous or compound heterozygous autosomal-recessive CHI to have a severe presentation and failed medical treatment and eventually undergo pancreatectomy.

Results

Conclusion