背景:先天性全身性脂肪营养不良(CGL)是一种罕见的遗传性疾病,其特征是几乎完全缺乏脂肪组织,并与器官系统异常和严重的代谢并发症有关。这里,我们分析了来自中东和北非(MENA)未接受脂肪营养不良特异性治疗的最大CGL队列的疾病特征.
方法:CGL是由治疗医生通过身体评估进行临床诊断的,并得到遗传分析的支持。脂肪流失模式,家族史,以及父母血缘关系的存在。数据是在患者诊断时和在可用医疗记录允许的瘦素替代初始随访期间获得的。
结果:数据来自43例CGL患者(37例女性,86%)是从八个国家/地区的中心收集的。平均值(中位数,range)诊断时的年龄为5.1(1.0,出生时37岁)。整个队列的遗传分析表明,CGL1(n=14,33%)和CGL2(n=18,42%)是主要的CGL亚型,其次是CGL4(n=10,23%);一名患者(2%)无法进行遗传诊断。有一个高患病率的父母血亲(93%)和家族史(67%)的脂肪营养不良,64%(n=25/39)和51%(n=20/39)的患者表现为肢端类特征和黑棘皮病,分别。81%(n=35/43)的患者至少有一个器官异常;最常见的受影响的器官是肝脏(70%,n=30/43),心血管系统(37%,n=16/43)和脾脏(33%,n=14/43)。28名患者中有13名(46%)的HbA1c>5.7%,20/33(61%)的甘油三酯水平>2.26mmol/L(200mg/dl)。一般来说,与儿童期诊断的患者相比,青春期或以后诊断的患者代谢疾病的严重程度更高;然而,在1岁之前或1岁时确诊的患者亚组中观察到代谢和器官系统异常.
结论:这项分析表明,除了早期脂肪减少外,家族史和高度血缘关系使MENA地区的年轻CGL患者得以识别。在没有接受脂肪营养不良特异性治疗的CGL患者中,严重的代谢疾病和器官异常可以在儿童晚期发展,并随着年龄的增长而恶化。
BACKGROUND: Congenital generalized lipodystrophy (CGL) is a rare inherited disease characterized by a near-total absence of adipose tissue and is associated with organ system abnormalities and severe metabolic complications. Here, we have analyzed the disease characteristics of the largest CGL cohort from the Middle East and North Africa (MENA) who have not received lipodystrophy-specific treatment.
METHODS: CGL was diagnosed clinically by treating physicians through physical assessment and supported by genetic analysis, fat loss patterns, family history, and the presence of parental consanguinity. Data were obtained at the time of patient diagnosis and during leptin-replacement naïve follow-up visits as permitted by available medical records.
RESULTS: Data from 43 patients with CGL (37 females, 86%) were collected from centers located in eight countries. The mean (median, range) age at diagnosis was 5.1 (1.0, at birth-37) years. Genetic analysis of the overall cohort showed that CGL1 (n = 14, 33%) and CGL2 (n = 18, 42%) were the predominant CGL subtypes followed by CGL4 (n = 10, 23%); a genetic diagnosis was unavailable for one patient (2%). There was a high prevalence of parental consanguinity (93%) and family history (67%) of lipodystrophy, with 64% (n = 25/39) and 51% (n = 20/39) of patients presenting with acromegaloid features and acanthosis nigricans, respectively. Eighty-one percent (n = 35/43) of patients had at least one organ abnormality; the most frequently affected organs were the liver (70%, n = 30/43), the cardiovascular system (37%, n = 16/43) and the spleen (33%, n = 14/43). Thirteen out of 28 (46%) patients had HbA1c > 5.7% and 20/33 (61%) had triglyceride levels > 2.26 mmol/L (200 mg/dl). Generally, patients diagnosed in adolescence or later had a greater severity of metabolic disease versus those diagnosed during childhood; however, metabolic and organ system abnormalities were observed in a subset of patients diagnosed before or at 1 year of age.
CONCLUSIONS: This analysis suggests that in addition to the early onset of fat loss, family history and high consanguinity enable the identification of young patients with CGL in the MENA region. In patients with CGL who have not received lipodystrophy-specific treatment, severe metabolic disease and organ abnormalities can develop by late childhood and worsen with age.