A compound heterozygous mutation of ABCC8 gene causing a diazoxide-unresponsive congenital hyperinsulinism with an atypical form: Not a focal lesion in the pancreas reported by ¹⁸F-DOPA-PET/CT scan

Gene. 2015 Nov 10;572(2):222-6. doi: 10.1016/j.gene.2015.07.012. Epub 2015 Jul 8.

Abstract

Congenital hyperinsulinism (CHI) is a severe heterogeneous disorder due to dysregulation of insulin secretion from the pancreatic β-cells leading to severe hypoglycemia in infancy. 18-fluoro-l-3,4-dihydroxyphenylalanine positron emission tomography ((18)F‑DOPA‑PET)/CT is a useful tool in distinguishing between focal and diffuse disease preoperatively. But recent studies have suggested that the scanning may not be accurate as initially estimated. In this study we characterize a case of CHI with a compound heterozygous mutation of ABCC8 gene. The results of clinical investigation, gene mutation analysis, (18)F‑DOPA‑PET/CT scan, and pathological examination showed some new characteristics that have never been reported. The patient was unresponsive to medical therapy with diazoxide and received pancreatectomy twice. Genetic analysis identified a compound heterozygous mutation in ABCC8 genes. Imaging with (18)F‑DOPA‑PET/CT indicated a focal lesion in the head of the pancreas. The pathological diagnosis was an atypical form of CHI. The patient presented with a phenotype of atypical CHI unresponsive to diazoxide. It is considered that a relationship existed between the compound heterozygous mutation and the atypical form. (18)F‑DOPA‑PET/CT is a useful tool in distinguishing between focal and diffuse forms preoperatively but the accuracy is not 100%. The scan result is best combined with genetic analysis and intra-operative biopsy to confirm the histological subtypes. The combination will provide the optimal strategy for the surgical treatment of patients with CHI.

Keywords: (18)F‑DOPA‑PET/CT; ABCC8 gene; Congenital hyperinsulinism.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Congenital Hyperinsulinism / genetics*
  • Congenital Hyperinsulinism / pathology*
  • Diagnosis, Differential
  • Dihydroxyphenylalanine / analogs & derivatives
  • Dihydroxyphenylalanine / metabolism
  • Heterozygote
  • Humans
  • Male
  • Mutation
  • Pancreas / pathology*
  • Positron-Emission Tomography / methods
  • Sulfonylurea Receptors / genetics*

Substances

  • ABCC8 protein, human
  • Sulfonylurea Receptors
  • fluorodopa F 18
  • Dihydroxyphenylalanine