Department of Pediatrics, Genetics Unit, Mansoura University Children's Hospital (MUCH), 31 Bank Misr Street, Mansoura 35516, Egypt.
Clin Exp Nephrol. 2012 Aug;16(4):604-10. doi: 10.1007/s10157-012-0603-9. Epub 2012 Feb 18.
Fanconi-Bickel syndrome (FBS) is an autosomal recessive disorder caused by defects in the facilitative glucose transporter 2 (GLUT2 or SLC2A2) gene which codes for the glucose transporter protein 2 expressed in hepatocytes and renal tubular cells causing a defect in carbohydrate metabolism, hepatomegaly, severe hypophosphatemic rickets and failure to thrive.
Among 17 unrelated Egyptian families with heritable renal tubular acidosis, three families clinically suspected as FBS were enrolled for this study after providing written informed consent. The three families had positive consanguinity and index cases with characteristic clinical features of FBS (hepatorenal glycogen accumulation, glucose and galactose intolerance, fasting hypoglycemia, a characteristic tubular nephropathy). Laboratory work-up included urinalysis, renal and liver function tests, fasting and postprandial blood sugar, serum calcium, phosphorus, alkaline phosphatase, sodium and potassium, lipid profile and arterial blood gas analysis. Imaging studies included bone survey and abdominal ultrasound. Liver biopsy was performed to confirm pathological diagnosis of the liver enlargement. Molecular analysis was performed for all family members-polymerase chain reaction followed by direct sequencing of the coding segments as well as the flanking introns.
Three different mutations were detected, one specific for each family, including two new mutations. In the first family, exon 3, two bases (GA) were deleted (c.253_254delGA causing a frameshift mutation (p. Glu85fs); the patient presented with early symptoms but unfortunately died despite adequate treatment. In the second family, a mutation was found in exon 6, in the splicing acceptor site with intron 5 (c.776-1G>C or IVS5-1G>A). The third family showed a missense mutation C-to-T substitution at c.1250 (c.1250C>T) causing change of codon 417 (CCG) for proline to CTG for leucine (p. P417L); this is a well-known mutation in the Arab population previously localized in exon 9; however, it is currently renumbered to exon 10.
Neither the new mutations nor the reported one were particularly more frequent; however, the third mutation (c.1250C>T) needs more attention in survey studies especially if performed in Arab patients as it has been renumbered because of the 'change' of gene structure since the initial reports.
范可尼-比克尔综合征（FBS）是一种常染色体隐性疾病，由葡萄糖转运蛋白 2（GLUT2 或 SLC2A2）基因缺陷引起，该基因编码在肝细胞和肾小管细胞中表达的葡萄糖转运蛋白 2，导致碳水化合物代谢缺陷、肝肿大、严重的低磷性佝偻病和生长不良。
在 17 个无关的遗传性肾小管酸中毒埃及家族中，有 3 个家族经临床怀疑为 FBS，在提供书面知情同意后，纳入本研究。这 3 个家族有阳性的近亲关系，且索引病例具有 FBS 的特征性临床特征（肝肾功能障碍、葡萄糖和半乳糖不耐受、空腹低血糖、特征性肾小管肾病）。实验室检查包括尿液分析、肾功能和肝功能检查、空腹和餐后血糖、血清钙、磷、碱性磷酸酶、钠和钾、血脂谱和动脉血气分析。影像学检查包括骨骼扫描和腹部超声。进行肝活检以确认肝肿大的病理诊断。对所有家族成员进行分子分析-聚合酶链反应（PCR），然后直接对编码片段以及侧翼内含子进行测序。
检测到 3 种不同的突变，每种突变均针对一个家族，包括 2 种新突变。在第一个家族中，第 3 外显子有 2 个碱基（GA）缺失（c.253_254delGA 导致移码突变（p.Glu85fs）；患者出现早期症状，但尽管进行了充分治疗，仍不幸死亡。在第二个家族中，在第 6 外显子的剪接受体位点发现了突变，在第 5 内含子（c.776-1G>C 或 IVS5-1G>A）。第三个家族显示 c.1250 处 C 到 T 的错义突变（c.1250C>T），导致密码子 417（CCG）脯氨酸突变为亮氨酸（CTG）（p.P417L）；这是阿拉伯人群中以前定位于第 9 外显子的一个已知突变；然而，由于基因结构的“变化”，它目前被重新编号为第 10 外显子。
新突变和已报道的突变都没有特别频繁；然而，第三个突变（c.1250C>T）在调查研究中需要更多的关注，特别是如果在阿拉伯患者中进行研究，因为自最初报道以来，由于基因结构的“变化”，它已经被重新编号。
