Identification of a diffuse form of hyperinsulinemic hypoglycemia by 18-fluoro-L-3,4 dihydroxyphenylalanine positron emission tomography/CT in a patient carrying a novel mutation of the HADH gene
Identification of a diffuse form of hyperinsulinemic hypoglycemia by 18-fluoro-L-3,4 dihydroxyphenylalanine positron emission tomography/CT in a patient carrying a novel mutation of the HADH gene
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DOI：
10.1530/eje-08-0945
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发表时间：
2009-06-01
影响因子：
5.8
通讯作者：
Mora, Stefano
中科院分区：
文献类型：
--
作者：
Di Candia, Stefania;Gessi, Alessandra;Mora, Stefano
目的：先天性高胰岛素血症是婴儿期持续性低血糖（HI）的最常见原因，如果不及时治疗，会导致严重的神经功能障碍。最近应用18-氟-L-3，4-二羟基苯丙氨酸正电子发射断层扫描（PET）/计算机断层扫描（CT）提高了区分HI两种组织病理学形式的能力（局灶性和弥漫性），其分化严重影响患者的治疗管理。病例报告：我们描述的情况下，病人提出了严重的低血糖从婴儿期高浓度的胰岛素建议诊断为先天性高胰岛素血症。未检测到与氨基酸、有机酸或脂肪酸氧化相关的代谢紊乱。看病结果：患者接受PET/CT扫描，显示弥漫性疾病。KCNJ 11和ABCC 8基因没有突变（50%的HI病例是由KCNJ 11和ABCC 8基因突变引起的）。全基因组单核苷酸多态性分析表明HADH基因可能是一个候选基因。结论：本病例提示，在高胰岛素血症患者中，即使在有机酸和酰基肉毒碱浓度无改变的情况下，当KCNJ 11和ABCC 8基因突变筛查阴性时，可推测为弥漫性HI和常染色体隐性遗传时，应寻找HADH基因的突变。
Objective: Congenital hyperinsulinism is the most common cause of persistent hypoglycemia in infancy (HI), leading to severe neurologic disabilities if not promptly treated. The recent application of positron emission tomography (PET)/computed tomography (CT) scanning with 18-fluoro-L-3,4 dihydroxyphertylalanine improved the ability to distinguish the two histopathologic forms of HI (focal and diffuse), whose differentiation heavily influences the therapeutic management of the patient.Case report: We describe the case of a patient presenting with severe hypoglycemia from infancy High concentration of insulin suggested the diagnosis of congenital hyperinsulinism. No metabolic disorders related to amino acid, organic acids or fatty acid oxidation were detected. Medical treatment. was able to obtain a satisfactory metabolic response.Results: The patient underwent PET/CT scanning, revealing a diffuse form of the disease. The absence of mutations in KCNJ11 and ABCC8 genes (responsible for 50%, of HI cases). and whole genome single nucleotide polymorphisms analysis by microarray suggested the HADH gene as a likely candidate. Sequence analysis revealed a novel homozygous nonsense mutation (R236X) in HADH gene.Conclusions: This case indicates that mutations of the HADH gene should be sought in hyperinsulinemic patients in whom diffuse form of HI and autosomal recessive inheritance can be presumed when KCNJ11 and ABCC8 genes mutational screening is negative, even in the absence of altered organic acids and acylcarnitines concentration.