脂肪營(yíng)養(yǎng)不良綜合征培訓(xùn)課件

1、 definition and classificationClinical Findings of the Major Lipodystrophy SubtypesClinical CharacteristicsstructureDiagnosisTherapies definition and classification definition andClassification definition A heterogeneous group of congenital or acquired disorders characterized by either complete or p

2、artial 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 definition3 definition3classification congenital generalized lipodystrophy (CGL)acquired generalized lipodystrop

3、hy (AGL)acquired partial lipodystrophy (APL)familial partial lipodystrophy (FPL)HAART-associated lipodystrophy syndromeclassification congenital gene CGL(先天性全身脂肪營(yíng)養(yǎng)不良), or Berardinelli-Seip syndrome（伯拉迪尼 - 塞普綜合征）, is an autosomal recessive常染色體隱性遺傳 disorder characterized by a generalized lack of adipo

4、se tissue at birth or shortly thereafter (within the first year of life), and is accompanied by prominent muscularity and subcutaneous veins . Congenital Generalized Lipodystrophy5 Congenital Generalized L In early childhood, patients with CGL may exhibit hyperphagia 食欲過(guò)盛(possibly a manifestation of

5、 underlying leptin deficiency), accelerated linear growth, advanced bone age骨齡超前, or acromegaloid features (enlarged hands, feet, and mandible), while later in childhood, acanthosis nigricans黑棘皮癥 can develop and become widespread . Hyperinsulinemia and hypertriglyceridemia高胰島素血癥和高甘油三酯血癥 can occur at

6、 an early age, with ketosis-resistant diabetes mellitus酮癥性糖尿病 usually developing later in adolescence. Congenital Generalized Lipodystrophy6 In early childhood, patie Hepatomegaly from severe hepatic steatosis is common and can progress to steatohepatitis脂肪性肝炎, cirrhosis, and liver failure. females

7、with CGL may have hirsutism, 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基因突變 AGPAT

8、2 and BSCL2. Congenital Generalized Lipodystrophy7 Hepatomegaly from severe h 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

9、-year-old boy with umbilical prominence and otherwise normal appearing muscular habitus. Congenital Generalized Lipody AGL(獲得性全身脂肪營(yíng)養(yǎng)不良), or Lawrence syndrome(勞倫斯綜合征), in contrast to CGL, patients with AGL are born with normal fat distribution but lose fat in a generalized fashion, typically starting

10、 in childhood or adolescence (rarely beginning after 30 years of age) acquired generalized lipodystrophy 9 AGL(獲得性全身脂肪營(yíng)養(yǎng)不良), or Lawr 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

11、 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 10 Progressive fat loss usual In some patients, the onset of AGL is heralded by the development of subcut

12、aneous inflammatory nodules皮下炎性結(jié)節(jié) (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特發(fā)性 (50%) on the basis of clinical findings. Auto

13、immune diseases, especially juvenile dermatomyositis兒童皮肌炎 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 lipodystrophy 1

14、1 In some patients, the onse 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 protub

15、erance. 12 acquired generalized lipodyst For both CGL and AGL, the presentation of diabetes in association with clinical evidence of insulin resistance胰島素抵抗 (e.g., high triglyceride levels) in a nonobese pediatric patient should serve as key distinguishing features from type 1 diabetes. it is import

16、ant to recognize that patients with all forms of generalized lipodystrophy can develop ketoacidosis酮癥酸中毒, especially under severe metabolic stress. generalized lipodystrophy 13 For both CGL and AGL, the FPL（家族性部分脂肪營(yíng)養(yǎng)不良） is predominantly inherited in an autosomal dominant 常染色體顯性遺傳fashion.Patients wit

17、h FPL usually have normal body fat distribution during infancy and early childhood, but, beginning 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 anter

18、ior abdomen and chest . Familial Partial Lipodystrophy14 FPL（家族性部分脂肪營(yíng)養(yǎng)不良） is predom Many patients (especially women) have fat accumulation in the face, neck, and intra-abdominal region, which may lead to a Cushingoid 類(lèi)庫(kù)欣appearance. Familial Partial Lipodystrophy15 Many patients (especially Diabetes

19、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 normally, although some may develop hirsutism多毛 and menstrual irregularities. Familial Partial Lipodystrophy16 Diabetes i

20、s more common a 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 肝脂肪變性和黑棘皮病may be less clinically impressive than that occurring in patients with generalized forms of lipodystrophy. Fin

21、ally, some patients with FPL may develop myopathy肌病, cardiomyopathy心肌病, and/or conduction system abnormalities傳導(dǎo)系統(tǒng)障礙。 Familial Partial Lipodystrophy17 Hypertriglyceridemia is a Familial Partial LipodystrophyFamilial partial lipodystrophy in 2 sisters. Both patients are in their early thirties. The p

22、atient 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).18 Familial Partial Lipodystroph APL（獲得性部分脂肪營(yíng)養(yǎng)不良） is characterized by a progressive loss of subc

23、utaneous 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代謝并發(fā)癥 are less common with APL than with other lipodystrophy

24、 subtypes亞型. Acquired Partial Lipodystrophy19 APL（獲得性部分脂肪營(yíng)養(yǎng)不良） is char The main cause of morbidity appears to be chronic renal disease (especially membranoproliferative glomeru- lonephritis膜性增生性腎小球腎炎). APL has also been associated with a number of autoimmune diseases, including dermatomyositis皮肌炎 an

25、d systemic lupus erythematosus系統(tǒng)性紅斑狼瘡. Most patients with APL have low levels of serum complement 3 (C3) accompanied by detectable levels of a circulating autoantibody自身抗體, C3 nephritic factor. APL is also more common in women than in men (estimated 4:1 ratio) Acquired Partial Lipodystrophy20 The ma

26、in cause of morbidi Acquired Partial Lipodystrophy21 Acquired Partial Lipodystroph HIV infection can occur in patients receiving highly fat nutrition during anti-retroviral therapy (highly active antiretroviral therapy, HAART)高效抗反轉(zhuǎn)錄病毒治療, especially when the application of HIV-1 protease inhibitor po

27、or HIV-1 蛋白酶抑制劑,the incidence of up to 40% to 70%, is the most common type of lipodystrophy . HAART-associated lipodystrophy syndrome22 HIV infection can occur i Although HAART significantly reduced mortality病死率 in patients with HIV infection, but HAART-related lipodystrophy (HAART-associated lipody

28、strophy 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 syndrome23 Although HAART signif

29、ican Risks associated 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 pa

30、thogenesis of HALS is not very clear, may be related to protease inhibitors (protease inhibitors, PIs蛋白酶抑制劑) of mitochondrial toxicity線(xiàn)粒體毒性, and PIs also by down-regulation of fat cell transcription factor (PPAR and C / EBP-) of the expression of fat cell differentiation. HAART-associated lipodystro

31、phy syndrome24 Risks associated with adva HAART-associated lipodystrophy syndrome25 HAART-associated lipodystroph Clinical Findings of the Major Lipodystrophy Subtypes26 Clinical Findings of the Majo Clinical Findings of the Major Lipodystrophy Subtypes27 Clinical Findings of the MajoClinical Charac

32、teristics 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 characterization, 5 of whom were eventually diag

33、nosed with FPL (3 with confirmed genetic mutations基因突變) .Clinical Characteristics InClinical Characteristics Although lipodystrophy is often accompanied by metabolic abnormalities代謝障礙, not all patients manifest them on presentation. Clinical laboratory testing (i.e., blood glucose, glycated hemoglob

34、in 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

35、 standard of care.Clinical Characteristics AltDiagnosis1.caliper measurements卡尺測(cè)量 of skinfold thickness皮膚褶皺厚度 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 infor

36、mation for the diagnosis of lipodystrophy.2.When fat loss is not visibly evident by physical manifestations, hyperglycemia高血糖 and hypertriglyceridemia高甘油三脂血癥 that are resistant or unresponsive to conventional treatment may serve as the only indication to the clinician that a patient may have lipodys

37、trophy.Diagnosis1.caliper measurementDiagnosis3.Lipodystrophy 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 lep

38、tin levels may be observed in other conditions (e.g., hypothalamic amenorrhea下丘腦性閉經(jīng)and malnutrition).4.lipodystrophy may also present with associated neuroendocrine神經(jīng)內(nèi)分泌 and immunological abnormalities免疫異常 (e.g., amenorrhea and a relative deficiency of T lymphocyte populationsT淋巴細(xì)胞缺乏) Diagnosis3.Lipodystrophy