目的 探讨早老症的临床表现及基因特征。 方法 收集北京协和医院2012年8月至2023年6月住院的11例早老症患者，提取相关临床资料，包括青春发育情况、糖代谢、脂代谢及既往心血管病变（动脉粥样硬化、心律失常、瓣膜病、心肌病）和治疗情况。分析早老症患者的早期临床表现及基因突变特征、实验室检查、青春发育状况，并对患者的糖脂代谢及心血管疾病进行评估。 结果 11例患者中，女性7例、男性4例，起病中位年龄3岁（1例为成人起病，其余为出生时或儿童青少年起病）。11例患者中半数以上有不同程度青春发育延迟，大部分患者有糖脂代谢异常，以胰岛素抵抗和低高密度脂蛋白胆固醇血症表现突出。心血管病变多见，3例患者为心肌广泛病变致心力衰竭，3例患者出现快速型或缓慢型心律失常，2例患者有动脉粥样硬化。5例患者完善基因检测，4例为核纤层蛋白A/C（LMNA）基因突变，均为非典型突变位点，分别为c.139G>T、c.1444C>A、c.398G>T、c.1045C>T，其中c.1444C>A尚未被报道；1例为RecQ3解旋酶（WRN）基因c.3913C>T突变。治疗上主要以针对糖脂代谢异常、心血管疾病等对症治疗为主。 结论 早老症患者临床表现多样，青春期及成人患者需进行青春发育、糖脂代谢及心血管病变评估，早期积极采取对症治疗。 Objective To explore the clinical manifestations, genetic characteristics, and treatment of progeria. Methods Clinical data of 11 progeria patients treated at Peking Union Medical College Hospital from August 2012 to June 2023 were collected, and clinical and genetic features were summarized, including pubertal development, glucose metabolism, lipid metabolism, previous cardiovascular lesions (atherosclerosis, cardiac arrhythmia, valvular disease, and cardiomyopathy) and treatment. Early clinical manifestations and gene mutation characteristics, laboratory tests, pubertal development, and assessment of glucose and lipid metabolism and cardiovascular disease in patients with progeria were analyzed. Results Of the 11 patients, 7 were female and 4 were male, with ages ranging from 9 to 37 years. One case had adult onset, while the rest had onset at birth or during childhood and adolescence. Majority of the patients had varying degrees of delayed puberty, and more than half had abnormalities in glucose and lipid metabolism, particularly insulin resistance, and markedly low high-density lipoprotein-cholesterol levels. Cardiovascular abnormalities were common, with 3 patients experiencing extensive myocardial damage leading to heart failure, 3 patients presenting with arrhythmia, and 2 patients showing atherosclerosis. Of the 5 patients who underwent comprehensive genetic testing, 4 had Lamin A/C (LMNA) gene mutations at non-typical mutation sites, namely c.139G>T, c.1444C>A, c.398G>T, and c.1045C>T. The c.1444C>A mutation has not been reported before, and 1 patient had a WRN gene c.3913C>T mutation. Treatment focused primarily on symptomatic interventions for abnormalities in glucose and lipid metabolism and cardiovascular diseases. Conclusions Progeria patients present with a variety of clinical manifestations. Adolescents and adults with progeria should pay attention to the assessment of puberty development, glucose and lipid metabolism, and cardiovascular abnormalities, and early intervention with targeted treatments is recommended.
Abstract
Objective To explore the clinical manifestations, genetic characteristics, and treatment of progeria. Methods Clinical data of 11 progeria patients treated at Peking Union Medical College Hospital from August 2012 to June 2023 were collected, and clinical and genetic features were summarized, including pubertal development, glucose metabolism, lipid metabolism, previous cardiovascular lesions (atherosclerosis, cardiac arrhythmia, valvular disease, and cardiomyopathy) and treatment. Early clinical manifestations and gene mutation characteristics, laboratory tests, pubertal development, and assessment of glucose and lipid metabolism and cardiovascular disease in patients with progeria were analyzed. Results Of the 11 patients, 7 were female and 4 were male, with ages ranging from 9 to 37 years. One case had adult onset, while the rest had onset at birth or during childhood and adolescence. Majority of the patients had varying degrees of delayed puberty, and more than half had abnormalities in glucose and lipid metabolism, particularly insulin resistance, and markedly low high-density lipoprotein-cholesterol levels. Cardiovascular abnormalities were common, with 3 patients experiencing extensive myocardial damage leading to heart failure, 3 patients presenting with arrhythmia, and 2 patients showing atherosclerosis. Of the 5 patients who underwent comprehensive genetic testing, 4 had Lamin A/C (LMNA) gene mutations at non-typical mutation sites, namely c.139G>T, c.1444C>A, c.398G>T, and c.1045C>T. The c.1444C>A mutation has not been reported before, and 1 patient had a WRN gene c.3913C>T mutation. Treatment focused primarily on symptomatic interventions for abnormalities in glucose and lipid metabolism and cardiovascular diseases. Conclusions Progeria patients present with a variety of clinical manifestations. Adolescents and adults with progeria should pay attention to the assessment of puberty development, glucose and lipid metabolism, and cardiovascular abnormalities, and early intervention with targeted treatments is recommended.
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