一种具有新型致病胰岛素基因变异的青年成熟型糖尿病的独特表型

JCEM case reports Pub Date : 2024-12-23 eCollection Date: 2025-01-01 DOI:10.1210/jcemcr/luae230
Cherie Chua, Clara Si Hua Tan, Su Chi Lim, Rashida Farhad Vasanwala
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摘要

青年成熟型糖尿病(MODY)占糖尿病(DM)患者的1%至5%,许多与MODY相关的基因已被确定。虽然已知胰岛素基因(INS)突变可导致永久性新生儿糖尿病,但在MODY中也发现了罕见的致病变异。这些患者表现出不同的临床表型-从需要生活方式或口服药物干预的轻度形式到需要终身胰岛素的严重形式。我们提出了一例由一种新的致病INS变异引起的MODY,在一个具有非典型特征的青少年中。他肥胖,临床表现为胰岛素抵抗,通过机会性口服葡萄糖耐量试验诊断为糖尿病。患者出现症状性高血糖,血糖趋势恶化,需要大剂量胰岛素和二甲双胍治疗。2年半后,他的血糖在体重减轻后恢复正常,并停止药物治疗。通过双向Sanger测序,靶向基因检测发现INS基因外显子2 (p.His29Tyr)有一个全新的错义变异。MODY患者的胰岛素抵抗可加重其临床病程并增加长期并发症的风险。这些患者的治疗应个体化。这个病例强调了基因检测在诊断罕见和可变形式的MODY,特别是那些具有非典型特征的MODY中的效用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A Unique Phenotype of Maturity-Onset Diabetes of the Young With a Novel Disease-Causing Insulin Gene Variant.

Maturity-onset diabetes of the young (MODY) represents 1% to 5% of patients with diabetes mellitus (DM), and numerous genes associated with MODY have been identified. While mutations of the insulin gene (INS) are known to cause permanent neonatal DM, rare disease-causing variants have also been found in MODY. These patients demonstrate variable clinical phenotypes-from milder forms requiring lifestyle or oral agent interventions to severe forms requiring lifelong insulin. We present a case of MODY arising from a novel disease-causing INS variant, in an adolescent with atypical features. He was obese with clinical evidence of insulin resistance, diagnosed with DM through opportunistic oral glucose tolerance testing. He developed symptomatic hyperglycemia with worsening glycemic trend, requiring treatment with high-dose insulin and metformin. After 2.5 years, his glycemic profile normalized following weight loss, and pharmacotherapy was discontinued. Targeted gene testing revealed a de novo novel missense variant in exon 2 of the INS gene (p.His29Tyr), confirmed using bidirectional Sanger sequencing. Insulin resistance in patients with MODY can worsen their clinical course and increase risks of long-term complications. Management of these patients should be individualized. This case highlights the utility of genetic testing in diagnosing uncommon and variable forms of MODY, particularly those with atypical features.

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