title: 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.
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.
authors.affiliation: Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou, China. Electronic address: liliuxia@hotmail.com.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wen
authors.affiliation: Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou, China.
authors.forename: Cuiling
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou, China.
authors.forename: Xiuzhen
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pathology, Guangzhou Women and Children's Medical Center, Guangzhou, China.
authors.forename: Huilin
authors.initials: H
authors.lastname: Niu
authors.affiliation: Department of Pathology, Guangzhou Women and Children's Medical Center, Guangzhou, China.
authors.forename: Fenghua
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou, China.
authors.forename: Huiying
authors.initials: H
authors.lastname: Sheng
authors.affiliation: Department of Radiology, Guangzhou Women and Children's Medical Center, Guangzhou, China.
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Liu
mesh_terms: D044903:Congenital Hyperinsulinism / Q000235:genetics* / Q000473:pathology*; D003937:Diagnosis, Differential; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010179:Pancreas / Q000473:pathology*; D049268:Positron-Emission Tomography / Q000379:methods; D064233:Sulfonylurea Receptors / Q000235:genetics*
chemical_list: C577507:ABCC8 protein, human; D064233:Sulfonylurea Receptors; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine
keywords: (18)F‑DOPA‑PET/CT; ABCC8 gene; Congenital hyperinsulinism