1、Lipodystrophy syndromes1 definition and classificationClinical Findings of the Major Lipodystrophy SubtypesClinical CharacteristicsstructureDiagnosisTherapies2 definition andClassification34 A heterogeneous group of congenital or acquired disorders characterized by either complete or partial lack of
2、 adipose tissue，which may occur in conjunction with pathological accumulation of fat in other distinct regions of the body，Belonged to the autonomic nervous system diseases definitionclassification congenital generalized lipodystrophy(CGL)acquired generalized lipodystrophy(AGL)acquired partial lipod
3、ystrophy(APL)familial partial lipodystrophy(FPL)HAART-associated lipodystrophy syndrome56 CGL(先天性全身脂肪营养不良),or Berardinelli-Seip syndrome（伯拉迪尼-塞普综合征）,is an autosomal recessive常染色体隐性遗传 disorder characterized by a generalized lack of adipose tissue at birth or shortly thereafter(within the first year o
4、f life),and is accompanied by prominent muscularity and subcutaneous veins.Congenital Generalized Lipodystrophy7 In early childhood,patients with CGL may exhibit hyperphagia 食欲过盛(possibly a manifestation of underlying leptin deficiency),accelerated linear growth,advanced bone age骨龄超前,or acromegaloid
5、 features(enlarged hands,feet,and mandible),while later in childhood,acanthosis nigricans黑棘皮症 can develop and become widespread.Hyperinsulinemia and hypertriglyceridemia高胰岛素血症和高甘油三酯血症 can occur at an early age,with ketosis-resistant diabetes mellitus酮症性糖尿病 usually developing later in adolescence.Con
6、genital Generalized Lipodystrophy8 Hepatomegaly from severe hepatic steatosis is common and can progress to steatohepatitis脂肪性肝炎,cirrhosis,and liver failure.females with CGL may have hirsutism,clitoromegaly,irregular menstrual periods,polycystic ovaries,and/or infertility.There are at least three ki
7、nds of disease-causing genes,clinically divided into three subtypes:CGL1,CGL2,CGL3.95%of CGL for the first two subtypes,and mutations associated基因突变 AGPAT2 and BSCL2.Congenital Generalized Lipodystrophy Congenital Generalized Lipodystrophy Congenital generalized lipodystrophy in A,a 6-month-old infa
8、nt with promi-nent muscularity and veins,B,a 16-year-old girl with acanthosis nigricans and umbilical prominence,C,a 15-year-old boy with umbilical prominence and otherwise normal appearing muscular habitus.910 AGL(获得性全身脂肪营养不良),or Lawrence syndrome(劳伦斯综合征),in contrast to CGL,patients with AGL are bo
9、rn with normal fat distribution but lose fat in a generalized fashion,typically starting in childhood or adolescence(rarely beginning after 30 years of age)acquired generalized lipodystrophy 11 Progressive fat loss usually occurs over a period of months to years,or as rapid as a few weeks for some p
10、atients,and affects large areas of the body,especially the face and extremities(including the palms and soles).Intra-abdominal fat loss is vari-able,and there may be sparing of bone marrow骨髓 and retroorbital眶后的 fat.acquired generalized lipodystrophy 12 In some patients,the onset of AGL is heralded b
11、y the development of subcutaneous inflammatory nodules皮下炎性结节(panniculitis);AGL occurs in approximately 3 times as many women as men.In a case series of 79 patients,AGL was classified into panniculitis-associated脂膜炎(25%of cases),autoimmune自身免疫(25%),and idiopathic types特发性(50%)on the basis of clinical
12、 findings.Autoimmune diseases,especially juvenile dermatomyositis儿童皮肌炎 and autoimmune hepatitis,occur commonly with AGL,suggesting that AGL could represent an autoimmune disease itself,but the inciting factors(autoantigens or effector mechanisms)remain to be elucidated.acquired generalized lipodystr
13、ophy 13 acquired generalized lipodystrophy Acquired generalized lipodystrophy(AGL)in A,a 19-year-old woman,B,a 9-year-old girl with juvenile dermatomyositis.Some common features among the 2 cases include lack of body fat and acanthosis nigricans,as well as abdominal protuberance.14 For both CGL and
14、AGL,the presentation of diabetes in association with clinical evidence of insulin resistance胰岛素抵抗(e.g.,high triglyceride levels)in a nonobese pediatric patient should serve as key distinguishing features from type 1 diabetes.it is important to recognize that patients with all forms of generalized li
15、podystrophy can develop ketoacidosis酮症酸中毒,especially under severe metabolic stress.generalized lipodystrophy 15 FPL（家族性部分脂肪营养不良）is predominantly inherited in an autosomal dominant 常染色体显性遗传fashion.Patients with FPL usually have normal body fat distribution during infancy and early childhood,but,begin
16、ning around or after puberty青春期,typically develop variable and progressive loss of subcutaneous fat in the arms and legs resulting in a peripheral muscular appearance with variable loss of fat in the anterior abdomen and chest.Familial Partial Lipodystrophy16 Many patients(especially women)have fat
17、accumulation in the face,neck,and intra-abdominal region,which may lead to a Cushingoid 类库欣appearance.Familial Partial Lipodystrophy17 Diabetes is more common and more severe in women than in men,particularly among multiparous women with excessive intra-abdominal fat deposition.Most affected women a
18、re able to reproduce normally,although some may develop hirsutism多毛 and menstrual irregularities.Familial Partial Lipodystrophy18 Hypertriglyceridemia is a common finding in FPL and can be severe,potentially leading to acute pancreatitis急性胰腺炎,while hepatic steatosis and acanthosis nigricans 肝脂肪变性和黑棘
19、皮病may be less clinically impressive than that occurring in patients with generalized forms of lipodystrophy.Finally,some patients with FPL may develop myopathy肌病,cardiomyopathy心肌病,and/or conduction system abnormalities传导系统障碍。Familial Partial Lipodystrophy19 Familial Partial LipodystrophyFamilial par
20、tial lipodystrophy in 2 sisters.Both patients are in their early thirties.The patient on the left has diabetes mellitus,while the patient on the right is nondiabetic.Note increased fat accumulation in the face and neck(A)with subcutaneous fat loss and muscularity in the arm(B).20 APL（获得性部分脂肪营养不良）is
21、characterized by a progressive loss of subcutaneous fat over months to years from the face,neck,arms,thorax,and upper abdomen during childhood or adolescence.Some patients may have excess fat accumulation over the lower abdomen,gluteal region,and legs.Metabolic complications代谢并发症 are less common wit
22、h APL than with other lipodystrophy subtypes亚型.Acquired Partial Lipodystrophy21 The main cause of morbidity appears to be chronic renal disease(especially membranoproliferative glomeru-lonephritis膜性增生性肾小球肾炎).APL has also been associated with a number of autoimmune diseases,including dermatomyositis皮
23、肌炎 and systemic lupus erythematosus系统性红斑狼疮.Most patients with APL have low levels of serum complement 3(C3)accompanied by detectable levels of a circulating autoantibody自身抗体,C3 nephritic factor.APL is also more common in women than in men(estimated 4:1 ratio)Acquired Partial Lipodystrophy22 Acquired
24、 Partial Lipodystrophy23 HIV infection can occur in patients receiving highly fat nutrition during anti-retroviral therapy(highly active antiretroviral therapy,HAART)高效抗反转录病毒治疗,especially when the application of HIV-1 protease inhibitor poor HIV-1 蛋白酶抑制剂,the incidence of up to 40%to 70%,is the most
25、common type of lipodystrophy.HAART-associated lipodystrophy syndrome24 Although HAART significantly reduced mortality病死率 in patients with HIV infection,but HAART-related lipodystrophy(HAART-associated lipodystrophy syndrome,HALS)and secondary metabolism AIDS treatment has become the most important a
26、dverse reactions.HALS general performance of the face,extremities,buttocks fat atrophy,and lower abdomen,neck and back fat accumulation.HAART-associated lipodystrophy syndrome25 Risks associated with advanced age HALS occur,the severity of HIV infection,the viral load increases,while low CD4 count a
27、nd viral hepatitis-related.HALS increased the incidence of AIDS in patients with insulin resistance,diabetes,dyslipidemia and cardiovascular 心血管疾病disease.The exact pathogenesis of HALS is not very clear,may be related to protease inhibitors(protease inhibitors,PIs蛋白酶抑制剂)of mitochondrial toxicity线粒体毒
28、性,and PIs also by down-regulation of fat cell transcription factor(PPAR and C/EBP-)of the expression of fat cell differentiation.HAART-associated lipodystrophy syndrome26 HAART-associated lipodystrophy syndrome27 Clinical Findings of the Major Lipodystrophy Subtypes28 Clinical Findings of the Major
29、Lipodystrophy SubtypesClinical Characteristics In one study of over 5000 Dutch patients with diabetes from 3 outpatient clinics where 2 screening criteria were applied(body mass index 27 kg/m2 and use of 100 units of insulin/day),12 out of 24 patients meeting these criteria had further characterizat
30、ion,5 of whom were eventually diagnosed with FPL(3 with confirmed genetic mutations基因突变).29Clinical Characteristics Although lipodystrophy is often accompanied by metabolic abnormalities代谢障碍,not all patients manifest them on presentation.Clinical laboratory testing(i.e.,blood glucose,glycated hemogl
31、obin HbA1c,triglyceride level甘油三酯,liver function studies肝功能,etc.)on initial evaluation of the patient with suspected lipodystrophy may still be useful for providing a baseline from which to monitor development of future metabolic abnormalities(if not already present),and should be considered the sta
32、ndard of care.30Diagnosis1.caliper measurements卡尺测量 of skinfold thickness皮肤褶皱厚度 may be helpful to quantify or characterize fat loss.Approximately 90%of adult men and women will have skinfold thickness values 10 mm and 22 mm;lower thickness values are supportive information for the diagnosis of lipod
33、ystrophy.2.When fat loss is not visibly evident by physical manifestations,hyperglycemia高血糖 and hypertriglyceridemia高甘油三脂血症 that are resistant or unresponsive to conventional treatment may serve as the only indication to the clinician that a patient may have lipodystrophy.31Diagnosis3.Lipodystrophy
34、is typically accompanied by low(or relatively low)levels of the adipocyte-secreted hormone leptin.leptin levels may provide useful supportive information,but are not necessary or specific for the diagnosis of lipodystrophy,as low leptin levels may be observed in other conditions(e.g.,hypothalamic am
35、enorrhea下丘脑性闭经and malnutrition).4.lipodystrophy may also present with associated neuroendocrine神经内分泌 and immunological abnormalities免疫异常(e.g.,amenorrhea and a relative deficiency of T lymphocyte populationsT淋巴细胞缺乏)32Therapies1.lifestyle modifications(diet and exercise)2.conventional antihyperglycemi
36、c and lipid-lowering edications Metformin二甲双胍,sulfonylureas磺脲类,thiazolidinediones噻唑烷二酮,and insulin can be used to manage hyperglycemia,while fibrates贝特类 and statins他汀类 can be used to manage hypertriglyceridemia.Where metabolic abnormalities代谢异常 associated with lipodystrophy are particularly severe,c
37、onventional treatments,alone or in combination,are likely to be inadequate at re-establishing metabolic control.33Therapies3.Plasmapheresis血浆置换 for lowering dangerously high triglyceride levels to control painful xanthoma黄瘤 and prevent pancreatitis胰腺炎.4.Leptin replacement therapy瘦素替代疗法 sustain reduc
38、tions in triglyceride甘油三酯,total cholesterol总胆固醇,and HbA1c levels.Metreleptin美曲普汀,a human leptin analog,is currently under review by the U.S.FDA for the treatment of certain metabolic abnormalities associated with lipodystrophy.34Therapies5.cosmetic美容 management of disfigurements(fat loss,fat redistribution,and outward manifestations of insulin resistance)that can severely impact patient self-image and sense of well-being.6.Roux-en-Y gastric bypass空肠-胃旁路手术35Thank you！36
