脂肪营养不良综合征Lipodystrophicsyndromes讲义.ppt

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,脂肪营养不良综合征Lipodystrophicsyndromes,Lipodystrophy is a medical condition characterized by complete or partial loss of adipose tissue.,In some of these disorders there is also the apparent accumulation of fat in other regions of the body,Introduction,Metabolic abnormalities,：,insulin resistance,diabetes mellitus,hypertriglyceridemia,hepatic steatosis,acanthosis nigricans,polycystic ovarian disease,hypertension,and proteinuric,kidney disease,The extent of fat loss correlates with the severity of the metabolic abnormalities.,脂肪组织营养不良表现,代谢活性脂肪组织丧失，伴有或不伴有机械保护性脂肪组织的丧失,假性肌肥大（由于皮下脂肪组织丧失而致肌肉组织外形毕露或由于肌肉内脂肪存积）,低瘦素、低脂联素水平伴食欲亢进,胰岛素抵抗及代谢紊乱,糖尿病或糖耐量异常，不伴酮症,严重高甘油三酯血症，反复发生胰腺炎,脂肪肝伴肝硬化,肌细胞及细胞间脂肪浸润,轻度高血压,临床特征,严重高胰岛素血症,黑棘皮,多囊卵巢综合征，月经失调、不育,卵巢高雄激素血症，女性男性化，多毛、阴蒂肥大,肢端肥大样表现，生长加速，但终身高正常或轻度增高,其他,骨骼畸形,肥厚心肌病,肾小球肾炎，蛋白尿,临床特征,全身性脂肪营养不良,先天性全身脂肪营养不良,(Congenital generalized lipodystrophy CGL),获得性全身脂肪营养不良,(Acquired generalized lipodystrophy AGL),部分脂肪营养不良,家族性部分脂肪营养不良,(Familial partial lipodystrophy FPLD),获得性部分脂肪营养不良,(Acquired partial lipodystrophy APL),获得性局部脂肪营养不良（,Acquired Localized lipodystrophy ALL,）,Lipodystrophy,的分类,1954,年由,Berardinelli,和,Seip,最先报道，故也称作,Seip-Berardinelli,综合征,为常染色体隐性遗传病，多发生在父母近亲结婚的后代,目前的文献报道大约有,250,例。,临床上分为,3,个亚型：,CGL1,、,CGL2,、,CGL3,。,95%,的,CGL,与,AGPAT2,和,BSCL2,基因突变相关,先天性全身性脂肪营养不良,(CGL),基因突变,染色体定位,临床特点,代谢紊乱,CGL1,AGPAT2,基因突变,(AR)AGPAT2,9q34,出生时或出生后不久发病，全身代谢性脂肪组织（皮下、骨髓、胸腔及腹腔）几乎完全消失，保护性脂肪（眶周、手掌、足底及关节周围）正常。,儿童期的食欲亢进，生长加速、高代谢及骨龄提前,黑棘皮、肝大，肌肉组织突出,严重的胰岛素抵抗；青少年发病的糖尿病；高甘油三酯血症,反复胰腺炎,脂肪肝,肝大,肝硬化,血清瘦素及脂联素水平下降,CGL2,BSCL2,基因突变,(AR),Seipin,11q13,代谢性脂肪组织及保护性脂肪均消失,代谢紊乱更严重，早产儿死亡率高，智力低下及心肌病发生率较高,CGL3,CAV1,的纯合突变（,AR),Caveolin1,7q31,与CGL1类似,症状严重程度介于二者之间,Both types are characterized by a generalized lack of fat,extreme muscularity,acanthosis nigricans in the groin and axillae,and acromegaloid features.Patients with CGL2 have a higher prevalence of intellectual impairment and cardiomyopathy than those with CGL1.,两种类型都表现为全身普遍脂肪缺乏，极度肌肉发达，黑棘皮征分布在腹股沟和腋窝，肢端肥大样表现。,CGL2,智能缺陷和心肌病发病率较,CGL1,高,1946,年,Lawerence,最先报道，又名,Lawerence,综合征,文献报道只有几十例，,F:M,3,：,1,发病机制：推测与自身免疫相关,皮下组织活检可发现脂膜炎,某些患者可检出抗脂肪细胞抗体,与其他自身免疫病并存,临床特征：儿童或成人发病，女性多见，多数青春期开始出现皮下脂肪减少，可累及面部、肢体、躯干及腹内脂肪，但眶后及骨髓腔内脂肪正常，肌肉组织逐渐显著，并逐渐出现肝大，多毛、黑棘皮及代谢紊乱,蛋白尿多见，肾活检提示局灶节段硬化或膜性增生性肾小球肾炎,获得性全身脂肪营养不良（,AGL),儿童、青少年期发病的区域性的脂肪萎缩，合并非萎缩部位的脂肪细胞异常肥大或增生。,合并胰岛素抵抗、高脂血症等代谢异常,部分有肥厚性心肌病及充血性心力衰竭表现,目前报道的基因突变类型至少有5种,家族性部分脂肪营养不良（FPLD）,FPLD type 2,的图例,Dunnigan variety,的,FPLD,，由于,LMNA,的错义突变，,LMNA,是编码,laminA,和,C,的基因，表现四肢和躯干的脂肪萎缩，面颈部的脂肪堆积，尤其是女性，可以有胸腹腔内脂肪堆积，使患者呈现库欣综合征样外貌,罕见的常染色体隐性遗传，文献报道约40例,TypeA与LMNA基因突变相关，四肢皮下脂肪组织减少，面部、颈部脂肪组织正常或增多，TypeB为全身皮下脂肪组织减少,特点：儿童或青春期发病，女性多见，合并生长迟滞，颅面骨畸形、关节痉挛、鸟样面容和牙齿异常，皮肤萎缩、脱发、色素沉着（早老表现），智力正常,代谢紊乱：高胰岛素血症、胰岛素抵抗、高脂血症、DM，瘦素水平可正常或偏低，个别有局灶性肾小球硬化，蛋白尿等,Mandibuloacral dysplasia,（,MAD),Frontal images shows narrow nose,full cheeks,and small jaw.The shoulders are sloping.Lateral shows beaked nose,small ear,and marked retrognathia.The hands show acrogeric skin changes,short distal phalanges and camptodactyly of the fifth fingers文献报道250例左右，大多数为欧洲人后裔,特点：面部、上身脂肪萎缩，其他部位脂肪堆积或正常,女性多见，儿童或青春期发病，F:M4-8：1,约2/3的患者循环补体C3水平降低，约20发生膜性增生性肾小球肾炎，4050在10年进展为ESRD，10可伴发其他自身免疫病,代谢紊乱：高胰岛素血症，DM发生率少（7%）,获得性部分性脂肪萎缩（,Barraquer-Simons syndrome,）,Human immunodeficiency virus(HIV)-infected individuals treated with highly active antiretroviral therapy(HAART)can develop lipodystrophy.,the most prevalent type of lipodystrophy，up to 4070%of patients on HAART are reported to have HIV-associated lipodystrophy syndrome,Wasting of the face,arms,legs,and buttocks,fat accumulation in the abdomen and dorsocervical area,Lipodystrophy associated with HIV therapy,Fat Redistribution in HIV-infected patients on HAART,HIV,感染的患在接受抗病毒治疗：面部、四肢的脂肪萎缩，而腹部脂肪的增多和水牛背、乳房增大。,获得性部分性脂肪萎缩：面颈部、上肢、胸部和上腹部的皮下脂肪萎缩下肢的脂肪过多。,获得性,GL,（,AGL,）：全身皮下脂肪的丧失开始于青春期，并发症包括严重的胰岛素抵抗、高胰岛素血症、高,TG,血症和低,HDL-C,characterized by a loss of subcutaneous fat from small areas of the body but not insulin resistance or other metabolic abnormalities.,Drug-induced,Presser-induced,as part of a rare syndrome called lipodystrophia centrifugalis abdominalis infantilis,Idiopathic,Localized lipodystrophies,脂肪营养不良病理生理机制和临床表现总结,Lifestyle Modification,Diet and Nutritional Therapy:,Exercise,Management of Diabetes,Metformin,Thiazolidinediones(TZDs),Management of Dyslipidemia,Statins,、,Fibrates,、,Niacin,、,Ezetimibe,Growth Hormone(GH)and Growth Hormone-releasing hormone(GHRH)analogs,Cosmetic treatment,Leptin replacement,治疗,Lipodystrophy is an umbrella term used to describe a diverse group of metabolic disorders characterized by either complete or partial loss of fat which may occur in conjunction with pathological accumulation of fat in other distinct regions of the body.,Patients with lipodystrophy suffer from numerous metabolic complications,There are no specific drugs for lipodystrophy.,SUMMARY,