背景:严重的胰岛素受体基因(INSR)相关的胰岛素抵抗综合征(SIR)包括Donohue综合征(DS),拉布森-门登霍尔综合征(RMS),和A型胰岛素抵抗。DS的发病率约为400万新生儿中的1。我们在SIR患者中发现了新的INSR突变(c.2246delG和c.2646+5G>A),这扩大了变异谱,并有助于提高对这种情况的诊断和治疗的理解。
方法:一名10岁的中国男孩因肤色加深而入院。他表现出生长迟缓,奇特的面部特征,黑棘皮病,多毛症,极高的胰岛素水平,空腹低血糖,和餐后高血糖,全外显子组基因测试表明INSR中存在复合杂合突变(c.2246delG和c.2646+5G>A)。
方法:诊断为SIR。更重要的是,根据表型和传记结果,这个孩子没有典型的RMS和DS,而是两种情况之间的中间表型.
方法:在合理饮食和锻炼的基础上,患者在早餐和午餐时服用二甲双胍(250毫克),1个月后增加到500毫克。
结果:治疗2个月后,患者的糖化血红蛋白(HbA1c)水平下降至6%,但胰岛素抵抗没有明显改善.
结论:在不肥胖但有严重胰岛素抵抗的儿童中,生长迟缓,多毛症,和高血糖,应进行基因检测以进行早期诊断,积极治疗,和后续行动。
BACKGROUND: Severe insulin receptor gene (INSR)-related insulin resistance syndromes (SIR) include Donohue syndrome (DS), Rabson-Mendenhall syndrome (RMS), and type A insulin resistance. The incidence of DS is about 1 in 4 million births. We identified novel INSR mutations (c.2246delG and c.2646 + 5G > A) in a patient with SIR, which expanded the variant spectrum and helped to improve the understanding of the diagnosis and treatment of this condition.
METHODS: A 10-year-old Chinese boy was admitted to the hospital for deepening skin color. He presented with growth retardation, peculiar facial features, acanthosis nigricans, hypertrichosis, extremely high insulin levels, fasting hypoglycemia, and postprandial hyperglycemia, Whole-exome gene testing suggested compound heterozygous mutations in INSR (c.2246delG and c.2646 + 5G > A).
METHODS: The diagnosis was SIR. What\'s more, based on the phenotypic and biographical results, this child did not present typical RMS and DS but rather an intermediate phenotype between the 2 conditions.
METHODS: On the basis of a sensible diet and exercise, the patient was prescribed metformin (250 mg) at breakfast and lunch, which was increased to 500 mg after 1 month.
RESULTS: After 2 months of treatment, the patient\'s glycated hemoglobin (HbA1c) levels decreased to 6% but his insulin resistance did not improve significantly.
CONCLUSIONS: In children who are not obese but with severe insulin resistance, growth retardation, hirsutism, and hyperglycemia, genetic testing should be performed for early diagnosis, active treatment, and follow-up.