Watanabe Daisuke, Yagasaki Hideaki, Narusawa Hiromune, Inukai Takeshi
Department of Pediatrics, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
Endocrinol Diabetes Metab Case Rep. 2024 Aug 1;2024(3). doi: 10.1530/EDM-23-0100. Print 2024 Jul 1.
Maturity-onset diabetes of the young (MODY) is a group of monogenic forms of diabetes mellitus characterized by early-onset diabetes with dominant inheritance of beta-cell dysfunction. There are few reports of the coinheritance of glucokinase (GCK) and hepatocyte nuclear factor 1 alpha gene (HNF1A) variants underlying MODY in patients. Herein, we describe a case involving combinations of monoallelic GCK and HNF1A variants associated with MODY. A 10-year-old Japanese girl with a three-generation family history of diabetes without obesity showed high levels of urinary glucose during a school screening test. Her glucose metabolism profile revealed 124 mg/dL of fasting glucose, 6.9% glycated hemoglobin (HbA1c), and 2.78 ng/mL of C-peptide immunoreactivity levels. In a 75-g oral glucose tolerance test, her base glucose, peak glucose, insulin resistance, and homeostasis model assessment of beta cell function levels were 124 mg/dL, 210 mg/dL (120 min), 1.71, and 33%, respectively. Based on the clinical phenotype of GCK-MODY, alimentary and exercise therapy without oral hypoglycemic agents were used to maintain her fasting glucose and HbA1c levels. We explored the coinheritance of MODY with GCK and HNF1A variants in this and past cases and found that careful clinical follow-up is required to firmly establish phenotypic features. Moreover, the accumulation of data on genetically confirmed MODY associated with the coinheritance of GCK and HNF1A variants will be useful for understanding genotype-phenotype correlations.
MODY is a group of monogenic forms of diabetes mellitus characterized by early-onset diabetes with the dominant inheritance of beta-cell dysfunction. MODY2 and MODY3 caused by heterozygous loss-of-function variants in the glucokinase (GCK) and hepatocyte nuclear factor 1 alpha (HNF1A) genes, respectively, are the most common forms of the disease. Few cases of MODY have previously been reported as being associated with the coinheritance of GCK and HNF1A variants. Careful clinical follow-up is required to firmly establish phenotypic features in the coinheritance of MODY with GCK and HNF1A variants. The accumulation of data on genetically confirmed MODY associated with the coinheritance of GCK and HNF1A variants will be useful for understanding genotype-phenotype correlations.
青年发病的成年型糖尿病（MODY）是一组单基因形式的糖尿病，其特征为早发性糖尿病伴β细胞功能障碍的显性遗传。关于患者中MODY潜在的葡萄糖激酶（GCK）和肝细胞核因子1α基因（HNF1A）变异共遗传的报道很少。在此，我们描述了一例涉及与MODY相关的单等位基因GCK和HNF1A变异组合的病例。一名10岁日本女孩，有三代糖尿病家族史，无肥胖，在学校筛查试验中尿糖水平较高。她的糖代谢谱显示空腹血糖为124mg/dL，糖化血红蛋白（HbA1c）为6.9%，C肽免疫反应水平为2.78ng/mL。在75g口服葡萄糖耐量试验中，她的基础血糖、峰值血糖、胰岛素抵抗和β细胞功能的稳态模型评估水平分别为124mg/dL、210mg/dL（120分钟）、1.71和33%。基于GCK-MODY的临床表型，采用饮食和运动疗法而非口服降糖药来维持她的空腹血糖和HbA1c水平。我们研究了该病例及既往病例中MODY与GCK和HNF1A变异的共遗传情况，发现需要仔细的临床随访才能确切确定表型特征。此外，积累与GCK和HNF1A变异共遗传相关的经基因证实的MODY数据将有助于理解基因型-表型相关性。
MODY是一组单基因形式的糖尿病，其特征为早发性糖尿病伴β细胞功能障碍的显性遗传。分别由葡萄糖激酶（GCK）和肝细胞核因子1α（HNF1A）基因的杂合功能丧失变异引起的MODY2和MODY3是该疾病最常见的形式。此前很少有MODY病例被报道与GCK和HNF1A变异的共遗传有关。在MODY与GCK和HNF1A变异的共遗传中，需要仔细的临床随访才能确切确定表型特征。积累与GCK和HNF1A变异共遗传相关的经基因证实的MODY数据将有助于理解基因型-表型相关性。
