Prader-Willi综合征儿童血瘦素水平变化趋势的研究

The tendency of age-related change of blood leptin levels in children with Prader-Willi syndrome

目的探讨Prader-Willi综合征(PWS)患儿年龄、进食对血瘦素水平的影响;寻找瘦素变化年龄节点,是否与过度摄食出现年龄相关。方法应用甲基化特异性PCR(methylation-specific PCR,MS-PCR)及甲基化特异性多重连接探针扩增(methylation-specific multiplex ligation-dependent probe amplification,MS-MLPA)方法对于2013年4月至2016年2月在北京协和医院儿科就诊的18岁以下28例PWS儿童进行诊断并分型,以年龄及性别匹配体检正常儿童作为对照组,检测2种遗传类型PWS患儿空腹及餐后2 h血瘦素水平,比较不同年龄、不同遗传类型患儿与正常对照组的差异。结果 28例PWS患儿中母源二体型9例,父源缺失型19例,空腹和(或)餐后2 h血瘦素水平的比较,父源缺失型与母源二体型PWS患儿空腹及餐后2 h瘦素水平差异无统计学意义;患儿空腹瘦素水平[1.08 ng/ml(0.37~8.06)ng/ml]显著高于正常对照组[0.38 ng/ml(0.37~2.24)ng/ml,P=0.001],且随年龄增长而呈上升趋势;患儿餐后2 h血瘦素水平比空腹时降低,降低值中位数为0.19 ng/ml(P=0.003);4.5岁(54个月)前患儿与正常对照组空腹血瘦素水平差异无统计学意义(P=0.054),4.5岁后患儿组显著增高(P=0.010)。结论 PWS患儿的血瘦素水平不受遗传类型的影响;患儿空腹血瘦素水平显著高于正常儿童,且随年龄增长而上升;4.5岁是PWS患儿血瘦素水平显著增高的时间界点,监测瘦素水平变化,可提示患儿过度摄食行为的出现而及时治疗。

Objective To explore the tendency of age-related change of blood leptin in children with Prader-Willi syndrome（PWS） and to understand the influence of feeding behavior to blood leptin in the patients, look for the turning point of leptin changing in PWS, and to identify if it is associated with the appearance of hyperphagia. Methods Twentyeight children under the age of 18 with PWS were diagnosed and classified by the genotypes using MS-PCR and MS-MLPA, who visited Peking Union Medical College Hospital from April 2013 to February 2016. Twenty-five healthy controls matched with PWS for age and gender were enrolled in the study. Fasting and postprandial 2 h circulating leptin levels were tested to compare the differences between the healthy controls and PWS children with different age, or different genetic types. Results In the 28 children with PWS, 9 were maternal uniparental disomy（m-UPD）, and 19 were paternal deletion. There was no significant difference between the two genetic types of PWS in fasting and postprandial leptin levels.The fasting leptin level in children with PWS [1.08 ng/ml（0.37~8.06 ng/ml）] was significantly higher than that of healthy control group [0.38 ng/ml（0.37~2.24 ng/ml）, P = 0.001], and increased along with the age growth. The postprandial leptin level was lower than fasting leptin levels in PWS children, the median reduced level was 0.19 ng/ml（P = 0.003）. There was no significant difference in fasting leptin levels between PWS children and healthy controls when they were under 4.5 years old（P = 0.054）. While, the fasting leptin level of PWS children was significantly higher than healthy controls after the age of 4.5（P = 0.010）. Conclusion The circulating leptin level of PWS children is not affected by the genetic types.Fasting leptin level of PWS is significantly higher than healthy controls, and increases along with the age growth. 4.5 years old is the inflection time point of significantly increased fasting leptin levels in children with PWS. We may find PWS appetite changes by monitoring the changes of leptin levels, and treat them timely.