PDF(Pubmed)
Abstract：
Morbidity and mortality rates in patients with autosomal recessive, congenital generalized lipodystrophy type 4 (CGL4), an ultra-rare disorder, remain unclear. We report on 30 females and 16 males from 10 countries with biallelic null variants in CAVIN1 gene (mean age, 12 years; range, 2 months to 41 years). Hypertriglyceridemia was seen in 79% (34/43), hepatic steatosis in 82% (27/33) but diabetes mellitus in only 21% (8/44). Myopathy with elevated serum creatine kinase levels (346-3325 IU/L) affected all of them (38/38). 39% had scoliosis (10/26) and 57% had atlantoaxial instability (8/14). Cardiac arrhythmias were detected in 57% (20/35) and 46% had ventricular tachycardia (16/35). Congenital pyloric stenosis was diagnosed in 39% (18/46), 9 had esophageal dysmotility and 19 had intestinal dysmotility. Four patients suffered from intestinal perforations. Seven patients died at mean age of 17 years (range: 2 months to 39 years). The cause of death in four patients was cardiac arrhythmia and sudden death, while others died of prematurity, gastrointestinal perforation, and infected foot ulcers leading to sepsis. Our study highlights high prevalence of myopathy, metabolic abnormalities, cardiac, and gastrointestinal problems in patients with CGL4. CGL4 patients are at high risk of early death mainly caused by cardiac arrhythmias.
摘要：
常染色体隐性遗传患者的发病率和死亡率，先天性全身性脂肪营养不良4型（CGL4），一种非常罕见的疾病，仍然不清楚。我们报告了来自10个国家的30名女性和16名男性在CAVIN1基因中具有双等位基因无效变异（平均年龄，12年；范围，2个月至41岁）。高甘油三酯血症见于79%(34/43)，肝脏脂肪变性占82%(27/33)，但糖尿病仅占21%(8/44)。血清肌酸激酶水平升高（346-3325IU/L）的肌病影响了所有患者（38/38）。39％患有脊柱侧凸（10/26），57％患有寰枢椎不稳定（8/14）。在57％（20/35）和46％的室性心动过速（16/35）中检测到心律失常。先天性幽门狭窄诊断为39%(18/46)，9例有食管运动障碍，19例有肠运动障碍。四名患者患有肠穿孔。7名患者死亡，平均年龄17岁（范围：2个月至39岁）。4例患者的死因是心律失常和猝死,而其他人死于早产,胃肠穿孔,和感染的足部溃疡导致败血症。我们的研究强调了肌病的高患病率，代谢异常，心脏,和CGL4患者的胃肠道问题。CGL4患者早期死亡的风险很高，主要由心律失常引起。
