先天性全身性脂肪营养不良一例

患儿女,4岁2个月,浙江青田人。因“面容特殊、多毛4年余”入院。外院及本院门诊曾诊断为“早老症”。患儿出生时即发现面容特殊,消瘦似“猴子”貌,全身多毛,以胸、背部及双下肢为重,皮肤较黑,出汗较多,无多饮多尿,进食可。平时体健,否认慢性腹泻史。第3胎第1产,足月剖腹出生,无窒息抢救史,出生体重3．0kg,周岁会走,2岁会叫爸爸、妈妈,现只能数10以内的数,不会讲故事。但身高一直较同龄儿高。父母体健,非近亲结婚。家族中无类似疾病患者。     

先天性全身脂肪营养不良一家系临床及基因变异分析

目的 探讨先天性全身脂肪营养不良症(CGL)的临床特征及基因变异特点.方法 回顾分析1对BSCL2基因变异致CGL双胎患儿的临床资料及其家系基因检测结果.结果 患儿均为男性,4月龄,均表现为全身脂肪组织消失,肝脾肿大,全身少量色素沉着.实验室检查示高三酰甘油血症.提取双胎中哥哥及父母的外周血,进行全外显子组基因测序并经...     

AGPAT2 基因变异致先天性全身脂肪营养不良症1 例报告并文献复习

目的分析AGPAT2基因变异致先天性全身脂肪不良症(CGL)的诊断和治疗。方法回顾分析1例AGPAT2基因变异致CGL患儿的临床资料、实验室检查及基因测序结果,并结合国内外文献进行分析总结。结果女性患儿,12岁,多饮多尿伴体质量下降1个月。患儿三角面容,皮下脂肪极少,肌肉发达,腋下黑棘皮症。实验室检查提示糖尿病、高脂血症以及脂肪肝。基因检测提示患儿AGPAT2基因复合杂合变异,c.379GC源自父亲,c.317-10TA源自母亲。根据美国医学遗传学与基因组学学会指南分析,c.379GC变异为疑似致病变异,c.317-10TA变异临床意义未明。患儿经皮下胰岛素注射及口服二甲双胍治疗后血糖控制可。结论该例为国内报道的第2例AGPAT2基因变异致CGL,且为新发现的基因变异。     

BSCL2 基因突变致先天性全身脂肪营养不良症1 例报告并文献复习

目的探讨先天性全身脂肪营养不良症(CGL)的临床及基因特点。方法回顾分析1例BSCL2基因突变致CGL患儿的临床资料,并进行文献复习。结果女性患儿,2岁9个月,临床表现为全身脂肪组织消失,黑棘皮征,肝脾大,轻度智力低下;实验室检查示高三酰甘油血症、高胰岛素血症和心肌病变。提取患儿及父母外周血,对AGPAT2、BSCL2、CAV1和PTRF 4个基因行Sanger测序显示,患儿存在BSCL2基因杂合突变,分别为母源移码突变(c.567-568del GA,p.E 189 Efs X 12)及父源无义突变(c.565 GT,p.E 189 X),均为致病突变。回顾文献,BSCL2基因突变是亚洲CGL最常见的病因,BSCL2突变的CGL患儿常见临床表现为全身脂肪组织消失、黑棘皮征和肝脾大,心肌病变和智力低下发生率分别为40%和30%。结论 BSCL2基因突变引起的CGL主要临床表现为自幼全身脂肪组织消失及代谢紊乱,常伴有心肌病变和智力低下,对疑似患儿应尽早行基因分析确诊。     

先天性脂肪肉瘤一例

患儿男,49ｄ。因发现颈部肿块1个月余入院。1个月前患儿母亲偶然发现其右颈部有一肿物,并逐渐长大。体检:右颈部肿物约5ｃｍ×6ｃｍ×4ｃｍ大小。表面皮肤呈暗蓝色,边界清楚。上极达乳突部,后至胸锁乳突肌,前至气管旁,下极至甲状软骨水平。气管居中,未发现浅表淋巴结肿大。胸、腹部ＣＴ检查未见异常。血常规:白细胞8.1×109/Ｌ,中性粒细胞0.34,单核细胞0.06;红细胞4.46×1012/Ｌ,血红蛋白128ｇ/Ｌ;血小板515×109/Ｌ。外科手术切除肿物,因肿物在大动脉周围未能被完全切除,术后病理报告为圆形细胞型脂肪肉瘤。家属放弃化疗,自动出院。脂肪肉…     

先天性及获得性脂肪营养不良北大核心CSCD

脂肪营养不良是多种原因导致的以机体脂肪组织不同程度缺失为主要特征的一组疾病,患者往往会合并多种代谢紊乱,如胰岛素抵抗、糖尿病、高三酰甘油血症和肝脏脂肪变性。通过可观察到的脂肪缺失程度和分布情况,本病可分为全身性、部分性和局部性3大类,而根据病因不同又进一步分为先天性和获得性2类。目前为止已报道了11个基因（ AGPAT2、BSCL2、CAVI、PTRF、PPARG、LMNA、ZMPSTE24、AKT2、CIDEC、PLINI、WRN）与先天性脂肪营养不良发病相关。最常见的获得性脂肪营养不良是长时间应用以蛋白水解酶抑制剂为核心药物的高效抗反转录病毒治疗所致的人类免疫缺陷病毒（HIV）感染者的脂肪营养不良。其他获得性脂肪营养不良与自身免疫有关,常伴补体异常。脂肪营养不良患者可以通过整容手术来改善外观,大部分患者在早期就出现多种代谢并发症,治疗上需要饮食、运动、降糖药和降脂药等多方面的配合,重组人瘦素类似物美曲普汀对治疗伴低瘦素血症的脂肪营养不良患者临床疗效显著,耐受性好。     

先天性肌营养不良伴脊柱强直一例

患儿女,9岁,因"进行性行走姿势异常8年,行走困难6年"入院.患儿1岁开始走路时发现行走姿势异常,腹部前凸,未予诊治.6年前(3～4岁)逐渐出现行走困难伴肢体无力,行走时双下肢屈曲,双足内旋,以右侧明显,易摔跤.渐加重,在1年内发展至小能独走,经按摩康复治疗后好转,能独走最多约3m.但病情仍进行性加重,近半年不能独走,能独坐,双上肢不能持萤,但日常生活不受影响.患儿姿势异常于立位时明显,睡眠时不能完全消失,平卧位腰部不能接触床面,双下肢不能伸直.     

先天性全身性脂肪营养不良BSCL2基因突变1例并文献复习

目的 报告1例先天性全身性脂肪营养不良（CGL）患儿的临床特点及随访情况,提高对该病的认识。 方法 分析1例CGL患儿病史、实验室检查和5年随访资料,对先证者及其父母行基因检测,系统复习国内外文献报告的CGL病例,归纳临床表型。 结果 男,5岁11个月,因“腹胀、消瘦5年余”就诊。患儿足月顺产,出生无窒息抢救史,5月龄会抬头,1岁会扶走。患儿1月龄渐出现腹胀、消瘦,2月龄渐出现皮下脂肪消失,肌肉渐发达,3~4月龄渐出现全身皮肤色素沉着,以颈部和腋下显著,5~6月龄渐出现全身皮肤毛发增多、增粗。查体：神清,空双颊,全身皮下脂肪消失,肌肉发达,四肢静脉血管显露。全身皮肤偏黑,多毛,颈部、腋下黑棘皮（+++）,皮肤弹性略差,心、肺查体未见异常,肝右肋下可扪及8 cm,质地中等。神经系统查体未见异常。智力测试72。双侧睾丸3 mL,阴茎5 cm×1.8 cm,阴毛Tanner 2期。父母体健,非近亲婚配。家族中无类似疾病患者。临床诊断先天性CGL,嘱低脂、高碳水化合物饮食。口服葡萄糖耐量试验提示糖耐量异常,予饮食控制。患儿BSCL2基因(NM_032667.6)存在：①错义突变c.713G>A, p.Gly238Asp（杂合）;②碱基重复c.782dupG, p.Ile262Hisfs*12（杂合）;其父亲携带错义突变c.713G>A, p.Gly238Asp（杂合）,母亲携带碱基重复c.782dupG, p.Ile262Hisfs*12（杂合）。经系统检索有10篇文献中的17例CGL患儿进入文献汇总分析,其临床主要特征：全身皮下脂肪消失、肌肉发达、皮下静脉显露、肢端肥大、多毛、黑棘皮症、高胰岛素血症、高甘油三酯血症、肝脾大、脂肪肝、肝功能异常和心肌病等。 结论 CGL罕见,易合并代谢性疾病。全身脂肪消失的患儿应首先考虑本病,基因确诊后应密切随访其代谢状况。本例患儿BSCL2基因携带的突变位点之一c.713G>A, p.Gly238Asp为首次报道。     

儿童全身性脂肪营养不良伴糖尿病1例报告

先天性全身脂肪营养不良(congenital generalizeslipodystrophy)由Berardinelli眼1演于1954年首先报道,1959年Seip眼2演又作了报道,故本病又名Berardinelli蛳Seip综合征(Berar鄄dinelli蛳Seip congenitallipodystrophy,BSCL),是非常少见的一种遗传代谢疾病,可存在糖耐量异常,合并糖尿病。儿童BSCL合并糖尿病国内尚未见报道,兹将此例报告如下。1临床资料男,7岁4个月,浙江人。因“自幼腹部膨隆,反复牙龈出血1年”入院。G1P1,足月顺产,无窒息抢救史,出生体重2250g。父母为表兄妹近亲结婚。生后母乳喂养至6个月,6个月后添加辅食。运动发…     

Triglyceride-induced diabetes mellitus in congenital generalized lipodystrophy

High levels of triglycerides and free fatty acids have been implicated in the pathogenesis of type 2 diabetes mellitus (DM). Congenital generalized lipodystrophy (CGL) is an autosomal recessive syndrome characterized by intense whole body reduction of subcutaneous fat. Its clinical manifestations appear during the first years of life. However, DM is usually a late event. We report a patient with CGL, diagnosed at 4 months of age, who has severe hypertriglyceridemia (serum triglyceride 12.34 mmol/l and cholesterol 3.90 mmol/l), muscular hypertrophy, hepatomegaly and DM (fasting glycemia 25.9 mmol/l). Hepatic biopsy revealed steatosis and fibrosis. A modified normolipidic (composed of medium chain triglycerides) normocaloric normoproteic milky diet and insulin therapy were instituted. After 1 month treatment a reduction of serum glucose and triglyceride levels (4.13 mmol/I and 7.7 mmol/l, respectively) was noted, with later normalization, which led to the discontinuation of insulin therapy. The patient has been maintaining good control with diet alone, presenting normal serum lipid levels (triglycerides 1.07 mmol/l, total cholesterol 2.71 mmol/l) and the following glycemic profile at OGTT: 0' 4.4 mmol/l; 30' 7.0 mmol/l; 60' 3.8 mmol/l; 90' 5.3 mmol/l, and 120' 5.2 mmol/l. The disappearance of hepatic steatosis was evidenced by a biopsy obtained 1 year after the beginning of treatment. In conolusion, this report suggests that the DM occurring in CGL can be precipitated by high triglyceride levels.     

Insulin receptor evaluation in congenital generalized lipodystrophy. Case report of an infant

Insulin specific receptors on red blood cells and cultured fibroblasts were investigated in a male infant affected of congenital generalized lipodystrophy (CGL). Total insulin binding capacity appeared mildly reduced, with apparently selective involvement of the high-affinity receptors on red blood cells but not on fibroblasts. Such alterations did not produce any impairment of glucose metabolism.     

Insulin resistance in a boy with congenital generalized lipodystrophy

We have studied insulin resistance in a 12-year-old Japanese boy who presented with congenital generalized lipodystrophy. Oral glucose tolerance test exhibited a diabetic pattern with normal fasting plasma glucose. Results from euglycemic glucose clamp study showed decreases in both insulin sensitivity and responsiveness. Both the patient's erythrocytes and Epstein-Barr virus transformed lymphocytes showed low-normal insulin binding with a slight reduction in binding affinity in the latter. Insulin binding to the cultured fibroblasts was decreased due to a lowered affinity. In addition, they displayed a rightward shift of the insulin dose-response curve for D-14C-glucose uptake with no decrease in the maximum uptake. Insulin-stimulated autophosphorylation and kinase activity of the wheat germ agglutinin purified receptors from the Epstein-Barr virus-transformed lymphocytes appeared normal. The reason for some discrepancies in insulin binding among the cells remains unknown, and we cannot formulate a conclusion as to whether or not a primary binding defect of insulin receptors exists and contributes to insulin resistance in the patient. The decrease in insulin responsiveness demonstrated in the glucose clamp study may result from a defect at the rate-limiting step in the postbinding process of insulin action, presumably a defect in the glucose transport system in muscle tissues. The defect may be secondary to changes in in vivo circumstances.     

Successful cardiac transplantation in a patient with congenital generalized lipodystrophy

We report a case of a 12‐yr‐old boy referred to our unit with congenital generalized lipodystrophy and dilated cardiomyopathy related to a lamin gene mutation. He progressively developed end‐stage heart failure and was referred for heart transplant evaluation. The patient's lipid profile, glucose level, and renal function were normal, and vascular retinopathy was ruled out. He underwent orthotopic bicaval HT and had an uneventful recovery. He was discharged home two wk after surgery with good graft function. During follow‐up, he developed hyperglycemia and dyslipidemia, which were controlled by increasing leptin dose and starting oral antidiabetic drugs. The patient is currently doing well two yr after transplantation.