Graduate Entry Medical School, Richmond Hill, Ontario, Canada.
J Hum Genet. 2014 Jan;59(1):16-23. doi: 10.1038/jhg.2013.107. Epub 2013 Oct 24.
Lipodystrophies are an immense group of genetic or acquired metabolic disorders that are characterized by varying degrees of body fat loss and in some instances localized accumulation of subcutaneous fat. Lipodystrophies are often tightly linked with profound metabolic complications; this strong bond emphasizes and reinforces the significance of adipose tissue as a dynamic endocrine organ. The extent of fat loss determines the severity of associated metabolic complications such as diabetes mellitus, hypertriglyceridemia and hepatic steatosis. The lipodystrophies can be divided into generalized, partial or local, depending on the degree and locality of the observable fat loss; moreover, the generalized and partial divisions can be partitioned further into inherited or acquired forms. The major genetic factors in the generalized forms of the lipodystrophies, particularly Congenital generalized lipodystrophy (CGL)-Berardinelli-Seip syndrome, are the AGPAT2, BSCL2, caveolin 1 (CAV1) and polymerase-I-and-transcriptrelease factor (PTRF) genes. In the acquired forms, genes such as LMNA, PPARG, CIDEC (cell-death-inducing DNA fragmentation factor a-like effector c) and PLIN1 are heavily involved in familial partial lipodystrophy (FPLD) type 2 (also known as the Dunnigan-Variety) and WRN along with RECQL5 in Werner Syndrome (WS). Autoimmune causes are particularly noted in acquired partial lipodystrophy (APL)-Barraquer-Simons syndrome and in AGL-Lawrence syndrome; panniculitis has been shown to have a substantial role in the former as well as in other forms of localized lipodystrophies. Patients with human immunodeficiency virus (HIV) exposed to protease inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs) (for example, zidovudine and stavudine) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) (for example, efavirenz) while undergoing Highly Active Antiretroviral Therapy (HAART) have led to the current most-prevalent form of the lipodystrophies: lipodystrophy in HIV-infected patients (LD-HIV) and HAART-associated lipodystrophy syndrome (HALS).
脂肪营养不良症是一组庞大的遗传性或获得性代谢紊乱疾病，其特征是不同程度的体脂丧失，在某些情况下还伴有局部皮下脂肪堆积。脂肪营养不良症常与严重的代谢并发症密切相关；这种紧密联系突出并强化了脂肪组织作为一个动态内分泌器官的重要性。脂肪丧失的程度决定了相关代谢并发症的严重程度，如糖尿病、高三酰甘油血症和肝脂肪变性。脂肪营养不良症可根据可观察到的脂肪丧失程度分为全身性、局部性或局部性；此外，全身性和局部性分类还可以进一步分为遗传性或获得性。在脂肪营养不良症的全身性形式中，AGPAT2、BSCL2、 caveolin 1（CAV1）和聚合酶-I-和转录释放因子（PTRF）基因是主要的遗传因素，特别是先天性全身性脂肪营养不良症（CGL）-Berardinelli-Seip 综合征。在获得性形式中，LMNA、PPARG、CIDEC（细胞死亡诱导 DNA 片段化因子 a 样效应因子 c）和 PLIN1 等基因在家族性部分脂肪营养不良症（FPLD）2 型（也称为 Dunnigan-Variety）和 WRN 以及 Werner 综合征（WS）中的 RECQL5 中起着重要作用。自身免疫性原因在获得性部分脂肪营养不良症（APL）-Barraquer-Simons 综合征和 AGL-Lawrence 综合征中尤为明显；在前者以及其他形式的局部性脂肪营养不良症中，脂膜炎已被证明具有重要作用。人类免疫缺陷病毒（HIV）患者在接受蛋白酶抑制剂、核苷逆转录酶抑制剂（NRTIs）（如齐多夫定和司他夫定）或非核苷逆转录酶抑制剂（NNRTIs）（如依法韦仑）进行高效抗逆转录病毒治疗（HAART）时，导致了目前最常见的脂肪营养不良症形式：HIV 感染患者的脂肪营养不良症（LD-HIV）和抗逆转录病毒治疗相关脂肪营养不良症综合征（HALS）。
