Rodríguez M A, Del Rio Barquero Luís M, Ortez Carlos I, Jou Cristina, Vigo Meritxell, Medina Julita, Febrer Anna, Ramon-Krauel Marta, Diaz-Manera Jorge, Olive Montse, González-Mera Laura, Nascimento Andres, Jimenez-Mallebrera Cecilia
Neuromuscular Unit, Department of Neuropaediatrics, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de DéuBarcelona, Spain.
Department of Medical Imaging, Hospital Sant Joan de DéuBarcelona, Spain.
Front Aging Neurosci. 2017 Aug 8;9:268. doi: 10.3389/fnagi.2017.00268. eCollection 2017.
Mutations in human collagen VI genes cause a spectrum of musculoskeletal conditions in children and adults collectively termed collagen VI-related myopathies (COL6-RM) characterized by a varying degree of muscle weakness and joint contractures and which include Ullrich Congenital Muscular Dystrophy (UCMD) and Bethlem Myopathy (BM). Given that collagen VI is one of the most abundant extracellular matrix proteins in adipose tissue and its emerging role in energy metabolism we hypothesized that collagen VI deficiency might be associated with alterations in adipose tissue distribution and adipokines serum profile. We analyzed body composition by means of dual-energy X-ray absorptiometry in 30 pediatric and adult COL6-RM myopathy patients representing a range of severities (UCMD, intermediate-COL6-RM, and BM). We found a distinctive pattern of regional adipose tissue accumulation which was more evident in children at the most severe end of the spectrum. In particular, the accumulation of fat in the android region was a distinguishing feature of UCMD patients. In parallel, there was a decrease in lean mass compatible with a state of sarcopenia, particularly in ambulant children with an intermediate phenotype. All children and adult patients that were sarcopenic were also obese. These changes were significantly more pronounced in children with collagen VI deficiency than in children with Duchenne Muscular Dystrophy of the same ambulatory status. High molecular weight adiponectin and leptin were significantly increased in sera from children in the intermediate and BM group. Correlation analysis showed that the parameters of fat mass were negatively associated with motor function according to several validated outcome measures. In contrast, lean mass parameters correlated positively with physical performance and quality of life. Leptin and adiponectin circulating levels correlated positively with fat mass parameters and negatively with lean mass and thus may be relevant to the disease pathogenesis and as circulating markers. Taken together our results indicate that COL6-RM are characterized by specific changes in total fat mass and distribution which associate with disease severity, motor function, and quality of life and which are clinically meaningful and thus should be taken into consideration in the management of these patients.
人类胶原蛋白VI基因的突变会导致儿童和成人出现一系列肌肉骨骼疾病，统称为胶原蛋白VI相关肌病（COL6-RM），其特征为不同程度的肌肉无力和关节挛缩，包括乌尔里希先天性肌营养不良（UCMD）和贝思伦肌病（BM）。鉴于胶原蛋白VI是脂肪组织中最丰富的细胞外基质蛋白之一，且其在能量代谢中的作用日益凸显，我们推测胶原蛋白VI缺乏可能与脂肪组织分布改变和脂肪因子血清谱变化有关。我们通过双能X线吸收法分析了30例儿科和成人COL6-RM肌病患者的身体成分，这些患者代表了一系列严重程度（UCMD、中间型COL6-RM和BM）。我们发现了一种独特的局部脂肪组织堆积模式，在病情最严重的儿童中更为明显。特别是，男性型区域脂肪堆积是UCMD患者的一个显著特征。与此同时，瘦体重减少，与肌肉减少症状态相符，尤其是在具有中间表型的能行走儿童中。所有患有肌肉减少症的儿童和成人患者也都肥胖。与相同行走状态的杜氏肌营养不良症儿童相比，胶原蛋白VI缺乏的儿童这些变化明显更显著。中间型和BM组儿童血清中高分子量脂联素和瘦素显著升高。相关性分析表明，根据几种经过验证的结果指标，脂肪量参数与运动功能呈负相关。相比之下，瘦体重参数与身体表现和生活质量呈正相关。瘦素和脂联素的循环水平与脂肪量参数呈正相关，与瘦体重呈负相关，因此可能与疾病发病机制有关，并可作为循环标志物。综上所述，我们的结果表明，COL6-RM的特征是总脂肪量和分布的特定变化，这些变化与疾病严重程度、运动功能和生活质量相关，具有临床意义，因此在这些患者的管理中应予以考虑。
