Ajluni Nevin, Meral Rasimcan, Neidert Adam H, Brady Graham F, Buras Eric, McKenna Barbara, DiPaola Frank, Chenevert Thomas L, Horowitz Jeffrey F, Buggs-Saxton Colleen, Rupani Amit R, Thomas Peedikayil E, Tayeh Marwan K, Innis Jeffrey W, Omary M Bishr, Conjeevaram Hari, Oral Elif A
Brehm Center for Diabetes Research and Division of Metabolism, Endocrinology & Diabetes, University of Michigan, Ann Arbor, MI, USA.
Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Clin Endocrinol (Oxf). 2017 May;86(5):698-707. doi: 10.1111/cen.13311. Epub 2017 Mar 27.
Partial lipodystrophy (PL) is associated with metabolic co-morbidities but may go undiagnosed as the disease spectrum is not fully described.
The objective of the study was to define disease spectrum in PL using genetic, clinical (historical, morphometric) and laboratory characteristics.
Cross-sectional evaluation.
Twenty-three patients (22 with familial, one acquired, 78·3% female, aged 12-64 years) with PL and non-alcoholic fatty liver disease (NAFLD).
Genetic, clinical and laboratory characteristics, body composition indices, liver fat content by magnetic resonance imaging (MRI), histopathological and immunofluorescence examinations of liver biopsies.
Seven patients displayed heterozygous pathogenic variants in LMNA. Two related patients had a heterozygous, likely pathogenic novel variant of POLD1 (NM002691·3: c.3199 G>A; p.E1067K). Most patients had high ratios (>1·5) of percentage fat trunk to percentage fat legs (FMR) when compared to reference normals. Liver fat quantified using MR Dixon method was high (11·3 ± 6·3%) and correlated positively with haemoglobin A1c and triglycerides while leg fat by dual-energy X-ray absorptiometry (DEXA) correlated negatively with triglycerides. In addition to known metabolic comorbidities; chronic pain (78·3%), hypertension (56·5%) and mood disorders (52·2%) were highly prevalent. Mean NAFLD Activity Score (NAS) was 5 ± 1 and 78·3% had fibrosis. LMNA-immunofluorescence staining from select patients (including one with the novel POLD1 variant) showed a high degree of nuclear atypia and disorganization.
Partial lipodystrophy is a complex multi-system disorder. Metabolic parameters correlate negatively with extremity fat and positively with liver fat. DEXA-based FMR may prove useful as a diagnostic tool. Nuclear disorganization and atypia may be a common biomarker even in the absence of pathogenic variants in LMNA.
部分脂肪营养不良（PL）与代谢合并症相关，但由于疾病谱尚未完全描述，可能未被诊断出来。
本研究的目的是利用遗传、临床（病史、形态测量）和实验室特征来定义PL的疾病谱。
横断面评估。
23例患有PL和非酒精性脂肪性肝病（NAFLD）的患者（22例为家族性，1例为获得性，78.3%为女性，年龄12 - 64岁）。
遗传、临床和实验室特征、身体成分指数、磁共振成像（MRI）测量的肝脏脂肪含量、肝活检的组织病理学和免疫荧光检查。
7例患者在LMNA基因中显示杂合致病性变异。两名相关患者有POLD1基因的杂合、可能致病性新变异（NM002691·3: c.3199 G>A；p.E1067K）。与参考正常人群相比，大多数患者的躯干脂肪百分比与腿部脂肪百分比之比（FMR）较高（>1.5）。使用MR Dixon方法量化的肝脏脂肪含量较高（11.3±6.3%），且与糖化血红蛋白和甘油三酯呈正相关，而通过双能X线吸收法（DEXA）测量的腿部脂肪与甘油三酯呈负相关。除了已知的代谢合并症外，慢性疼痛（78.3%）、高血压（56.5%）和情绪障碍（52.2%）也非常普遍。平均NAFLD活动评分（NAS）为5±1，78.3%的患者有肝纤维化。部分患者（包括1例携带新POLD1变异的患者）的LMNA免疫荧光染色显示高度的核异型性和紊乱。
部分脂肪营养不良是一种复杂的多系统疾病。代谢参数与四肢脂肪呈负相关，与肝脏脂肪呈正相关。基于DEXA的FMR可能是一种有用的诊断工具。即使在LMNA基因无致病性变异的情况下，核紊乱和异型性可能也是一种常见的生物标志物。
