Height as a Clinical Biomarker of Disease Burden in Adult Mitochondrial Disease
Height as a Clinical Biomarker of Disease Burden in Adult Mitochondrial Disease
复制标题
DOI：
10.1210/jc.2018-00957
复制
发表时间：
2019-06-01
影响因子：
5.8
通讯作者：
McFarland, Robert
中科院分区：
文献类型：
--
作者：
Boal, Rachel L.;Ng, Yi Shiau;McFarland, Robert
内容：在线粒体疾病患者中观察到异常生长和身材矮小，但目前尚不清楚最终成年身高与疾病严重程度之间是否存在关系。目的：确定遗传学证实的线粒体疾病患者是否比同龄人矮，以及身高是否与疾病严重程度相关。设计：根据纽卡斯尔线粒体疾病成人量表（NMDAS）确定的疾病严重程度，分析最终成人身高。患者：在Mito队列中，确定了575名记录有身高、体重和线粒体疾病分子遗传学诊断的患者。主要结果测量：成人身高、体重指数（BMI）及其与遗传亚组和疾病严重程度的相关性。与英国参考数据相比，患有线粒体疾病的成人身材矮小，平均身高为-0.49 SD（95% CI，-0.58至-0.39; n = 575）。患者超重，BMI SD为0.52（95% CI，0.37 - 0.67; n = 472）。最常见的遗传亚组（m.3243A>G突变）的身高SD为-0.70（95% CI，-0.85至-0.54; n = 234），BMI SD为0.12（95% CI，-0.10至0.34; n = 212）。NMDAS评分与身高SD呈负相关（r= -0.25; 95%CI，-0.33 ~-0.17; P < 0.001，n = 533）。疾病进展速度与成人身高呈负相关（P < 0.001）。结论：线粒体疾病的最终身高反映了疾病的严重程度和疾病进展速度。线粒体功能障碍和相关的亚临床合并症影响生长板生理学。
Context: Abnormal growth and short stature are observed in patients with mitochondrial disease, but it is unclear whether there is a relationship between final adult height and disease severity.Objective: To determine whether patients with genetically confirmed mitochondrial disease are shorter than their peers and whether stature is related to disease severity.Design: Analysis of final adult height in relation to disease severity as determined by the Newcastle Mitochondrial Disease Adult Scale (NMDAS).Setting: UK Mitochondrial Disease Patient Cohort (Mito Cohort).Patients: 575 patients were identified with recorded height, weight, and molecular genetic diagnosis of mitochondrial disease within the Mito Cohort.Main Outcome Measures: Adult height, body mass index (BMI), and their association with genetic subgroup and disease severity.Results: Adults with mitochondrial disease were short, with a mean height of -0.49 SD (95% CI, -0.58 to -0.39; n = 575) compared with UK reference data. Patients were overweight, with a BMI SD of 0.52 (95% CI, 0.37 to 0.67; n = 472). The most common genetic subgroup (m.3243A>G mutation) had a height SD of -0.70 (95% CI, -0.85 to -0.54; n = 234) and a BMI SD of 0.12 (95% CI, -0.10 to 0.34; n = 212). NMDAS scores were negatively correlated with height SD (r= -0.25; 95% CI, -0.33 to -0.17; P < 0.001, n = 533). Rate of disease progression also correlated negatively with adult height (P < 0.001).Conclusion: Final height in mitochondrial disease reflects disease severity and rate of disease progression. Mitochondrial dysfunction and associated subclinical comorbidities affect growth plate physiology.