脂肪营养不良综合征PPT课件

1、2021/6/71 Lipodystrophy syndromes 2021/6/72 definition and classification Clinical Findings of the Major Lipodystrophy Subtypes Clinical Characteristics structure Diagnosis Therapies 2021/6/73 definition and Classification 2021/6/74 A heterogeneous group of congenital or acquired disorders character

2、ized by either complete or partial lack of 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 definition 2021/6/75 classification congenital generalized lipodystrophy (CGL) acqu

3、ired generalized lipodystrophy (AGL) acquired partial lipodystrophy (APL) familial partial lipodystrophy (FPL) HAART-associated lipodystrophy syndrome 2021/6/76 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 l

4、ack of adipose tissue at birth or shortly thereafter (within the first year of life), and is accompanied by prominent muscularity and subcutaneous veins . Congenital Generalized Lipodystrophy 2021/6/77 In early childhood, patients with CGL may exhibit hyperphagia 食欲过盛(possibly a manifestation of und

5、erlying leptin deficiency), accelerated linear growth, advanced bone age骨龄超前, or acromegaloid 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

6、 early age, with ketosis-resistant diabetes mellitus酮症性糖尿病 usually developing later in adolescence. Congenital Generalized Lipodystrophy 2021/6/78 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 h

7、irsutism, clitoromegaly, irregular menstrual periods, polycystic ovaries, and/or infertility .There are at least three kinds 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. Conge

8、nital Generalized Lipodystrophy 2021/6/79 Congenital Generalized Lipodystrophy Congenital generalized lipodystrophy in A, a 6-month-old infant 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 promine

9、nce and otherwise normal appearing muscular habitus. 2021/6/710 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 born with normal fat distribution but lose fat in a generalized fashion, typically starting in childhood or adolescence (rarely beginning after 30

10、 years of age) acquired generalized lipodystrophy 2021/6/711 Progressive fat loss usually occurs over a period of months to years, or as rapid as a few weeks for some patients, and affects large areas of the body, especially the face and extremities (including the palms and soles).Intra-abdominal fa

11、t loss is vari- able, and there may be sparing of bone marrow骨 髓 and retroorbital眶后的 fat. acquired generalized lipodystrophy 2021/6/712 In some patients, the onset of AGL is heralded by the development of subcutaneous inflammatory nodules皮下炎性结节 (panniculitis); AGL occurs in approximately 3 times as

12、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 findings. Autoimmune diseases, especially juvenile dermatomyositis儿童皮肌 炎 and autoimmune hepatitis, occ

13、ur 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 lipodystrophy 2021/6/713 acquired generalized lipodystrophy Acquired generalized lipodystrophy (AGL) i

14、n 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. 2021/6/714 For both CGL and AGL, the presentation of diabetes in association with clinical eviden

15、ce 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 lipodystrophy can develop ketoacidosis酮症酸中毒, especially under seve

16、re metabolic stress. generalized lipodystrophy 2021/6/715 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, beginning around or after puberty青春期, typically develop

17、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 Lipodystrophy 2021/6/716 Many patients (especially women) have fat accumulation in the face, neck, and i

18、ntra- abdominal region, which may lead to a Cushingoid 类库欣appearance. Familial Partial Lipodystrophy 2021/6/717 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 are able to reproduce

19、 normally, although some may develop hirsutism多毛 and menstrual irregularities. Familial Partial Lipodystrophy 2021/6/718 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 肝脂肪变性和黑棘皮病may b

20、e 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 Lipodystrophy 2021/6/719 Familial Partial Lipodystrophy Fami

21、lial partial 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). 2021/6

22、/720 APL（获得性部分脂肪营养不良） is 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 compl

23、ications代谢并发症 are less common with APL than with other lipodystrophy subtypes亚型. Acquired Partial Lipodystrophy 2021/6/721 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

24、autoimmune diseases, including dermatomyositis皮肌炎 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 (estimate

25、d 4:1 ratio) Acquired Partial Lipodystrophy 2021/6/722 Acquired Partial Lipodystrophy 2021/6/723 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 protea

26、se inhibitor poor HIV-1 蛋白酶抑制剂, the incidence of up to 40% to 70%, is the most common type of lipodystrophy . HAART-associated lipodystrophy syndrome 2021/6/724 Although HAART significantly reduced mortality病死率 in patients with HIV infection, but HAART-related lipodystrophy (HAART-associated lipodys

27、trophy syndrome, HALS) and secondary metabolism AIDS treatment has become the most important adverse reactions. HALS general performance of the face, extremities, buttocks fat atrophy, and lower abdomen, neck and back fat accumulation. HAART-associated lipodystrophy syndrome 2021/6/725 Risks associa

28、ted with advanced age HALS occur, the severity of HIV infection, the viral load increases, while low CD4 count and 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 HAL

29、S 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 syndrome 202

30、1/6/726 HAART-associated lipodystrophy syndrome 2021/6/727 Clinical Findings of the Major Lipodystrophy Subtypes 2021/6/728 Clinical Findings of the Major Lipodystrophy Subtypes 2021/6/729 Clinical Characteristics In one study of over 5000 Dutch patients with diabetes from 3 outpatient clinics where

31、 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 characterization, 5 of whom were eventually diagnosed with FPL (3 with confirmed genetic mutations基 因突变) . 2021/6/730 Clinical Characteristics A

32、lthough 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 hemoglobin HbA1c, triglyceride level甘油三酯, liver function studies肝功能, etc.) on initial evaluation of the patient with s

33、uspected 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 standard of care. 2021/6/731 Diagnosis 1.caliper measurements卡尺测量 of skinfold thickness皮肤褶皱厚 度 may be helpful

34、 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 lipodystrophy. 2.When fat loss is not visibly evident by physical manifestations, hyperglycemia高

35、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. 2021/6/732 Diagnosis 3.Lipodystrophy is typically accompanied by low (or relatively low) levels of the adipocyte-se

36、creted 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 amenorrhea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) 2021/6/7