高血糖症幼儿中的葡萄糖激酶突变
Glucokinase mutations in young children with hyperglycemia.
作者信息
Codner Ethel, Deng Liyong, Pérez-Bravo Francisco, Román Rossana, Lanzano Patricia, Cassorla Fernando, Chung Wendy K
机构信息
Institute of Maternal and Child Research (I.D.I.M.I.), School of Medicine, University of Chile, Santiago, Chile.
出版信息
Diabetes Metab Res Rev. 2006 Sep-Oct;22(5):348-55. doi: 10.1002/dmrr.622.
BACKGROUND
The etiology of mild hyperglycemia without ketoacidosis in young children is often unknown. Maturity onset diabetes of youth (MODY) is a form of diabetes mellitus (DM) characterized by fasting hyperglycemia without evidence for autoimmune destruction of beta-cells.
METHODS
We genetically analyzed four families of young children with fasting hyperglycemia with family histories of diabetes for mutations in the genes for hepatocyte nuclear factor 4 alpha (HNF4alpha), glucokinase (GCK), and hepatocyte nuclear factor 1 alpha (HNF1alpha), the genes responsible for MODY1, MODY2, and MODY3, respectively.
RESULTS
We identified mutations in GCK (Gly258Asp, Arg303Trp, and Arg191Gln) in three of the four families. Molecular genetic characterization in these children clarified the etiology and prognosis of the hyperglycemia and allowed discontinuation of insulin therapy in one family.
CONCLUSIONS
We conclude that molecular evaluation for MODY in children with mild fasting hyperglycemia without ketosis with family histories of diabetes can provide important prognostic information to guide therapy and exclude preclinical type 1 diabetes mellitus.
背景
幼儿无酮症的轻度高血糖病因通常不明。青年发病的成年型糖尿病（MODY）是糖尿病（DM）的一种形式，其特征为空腹高血糖，且无β细胞自身免疫性破坏的证据。
方法
我们对四个有糖尿病家族史的空腹高血糖幼儿家庭进行了基因分析，检测肝细胞核因子4α（HNF4α）、葡萄糖激酶（GCK）和肝细胞核因子1α（HNF1α）基因的突变，这些基因分别是导致MODY1、MODY2和MODY3的基因。
结果
我们在四个家庭中的三个家庭中发现了GCK基因的突变（甘氨酸258天冬氨酸、精氨酸303色氨酸和精氨酸191谷氨酰胺）。对这些儿童的分子遗传学特征分析明确了高血糖的病因和预后，并使一个家庭得以停用胰岛素治疗。
结论
我们得出结论，对无酮症且有糖尿病家族史的轻度空腹高血糖儿童进行MODY分子评估，可为指导治疗提供重要的预后信息，并排除临床前期1型糖尿病。
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