Dusátková Petra, Průhová Stepánka, Sumník Zdenek, Kolousková Stanislava, Obermannová Barbora, Cinek Ondrej, Lebl Jan
Department of Pediatrics, University Hospital Motol and Second Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
J Pediatr Endocrinol Metab. 2011;24(5-6):377-9.
HNF1A-MODY (MODY3) is a common subtype of autosomal dominant diabetes. Unlike HNF4-MODY where fetal macrosomia and early postnatal hyperinsulinemic hypoglycemia have been reported, a history of transient insulin overproduction has not been recognized in individuals with HNF1A-MODY yet.
Here, we report a 40-year-old male patient with HNFJA mutation p.Arg272His (c.815G>A) with a history of fetal macrosomia (4750 g, 59 cm) and, at least, one attack of symptomatic hypoglycemia in childhood. Diabetes was subsequently diagnosed at 19 years. The proband's daughter who developed diabetes at 16 years carries the same mutation, but her birth weight and length were in the upper normal range, and she never experienced hypoglycemic symptoms.
The observation of fetal macrosomia and hypoglycemia in childhood is suggestive of a biphasic impact of the HNF1A mutation on beta-cell function over the lifespan, leading from inappropriate insulin oversecretion to final clinical diabetes.
肝细胞核因子1A - 成年发病型糖尿病（HNF1A - MODY，MODY3）是常染色体显性糖尿病的常见亚型。与已报道有巨大胎儿和出生后早期高胰岛素血症性低血糖的肝细胞核因子4 - 成年发病型糖尿病不同，肝细胞核因子1A - MODY患者尚未发现有短暂性胰岛素过度分泌的病史。
在此，我们报告一名40岁男性患者，其肝细胞核因子1A（HNF1A）发生p.Arg272His（c.815G>A）突变，有巨大胎儿病史（4750克，59厘米），且童年期至少有一次症状性低血糖发作。随后在19岁时被诊断为糖尿病。先证者16岁患糖尿病的女儿携带相同突变，但她出生时体重和身长处于正常范围上限，且从未出现过低血糖症状。
观察到巨大胎儿和儿童期低血糖提示HNF1A突变在整个生命周期对β细胞功能有双相影响，从胰岛素分泌不当到最终临床糖尿病。
