Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children's Memorial Health Institute.
Department of Genetics, Institute of Psychiatry and Neurology, Warsaw, Poland.
J Pediatr Gastroenterol Nutr. 2018 Oct;67(4):452-457. doi: 10.1097/MPG.0000000000002084.
Lysosomal acid lipase deficiency (LAL-D) is a rare autosomal recessive lysosomal lipid storage disorder that results in an early-onset, severe, and lethal phenotype, known as Wolman disease, or a late-onset, attenuated phenotype, cholesteryl ester storage disease (CESD). The aim of our study was to describe the clinical presentation of CESD, focusing on the first noted abnormalities in patients. A diagnostic algorithm of CESD was also proposed.
This is an observational, 1-center study of 19 Polish patients with late-onset LAL-D.
The mean age at which the first symptoms were reported was 4 years and 6 months. A mild hepatomegaly was the most common initial abnormality observed in all (100%) patients. Seven (37%) patients were noted to have mildly to moderately elevated serum transaminases. At the time of first hospitalization all (100%) patients presented with hepatomegaly, 15 (79%) patients presented with elevated serum transaminases and all (100%) patients had dyslipidemia. The mean age at the time of CESD diagnosis was 7 years and 2 months. Diagnoses were based on a deficient LAL activity in leukocytes (in all patients) and the LIPA gene mutations (in 47% of them). All the patients were carriers for the mutation c.894G>A in the LIPA gene. There was approximately a 3-year delay from initial symptoms to final diagnosis.
Hepatomegaly constitutes the most common presenting clinical sign of CESD. Hepatomegaly and dyslipidemia defined as elevated serum total and LDL cholesterol, elevated triglycerides and normal to low HDL cholesterol, comprises the most characteristic findings at CESD diagnosis.
溶酶体酸性脂肪酶缺乏症（LAL-D）是一种罕见的常染色体隐性溶酶体脂质贮积病，导致早发、严重和致命表型，称为沃曼病，或晚发、衰减表型，胆固醇酯贮积症（CESD）。本研究的目的是描述 CESD 的临床表现，重点介绍患者首次注意到的异常。还提出了 CESD 的诊断算法。
这是一项针对 19 名波兰晚发性 LAL-D 患者的观察性单中心研究。
首次报告症状的平均年龄为 4 岁零 6 个月。所有患者（100%）均出现轻度肝肿大，这是最常见的初始异常。7 名（37%）患者的血清转氨酶轻度至中度升高。首次住院时，所有患者（100%）均有肝肿大，15 名（79%）患者有血清转氨酶升高，所有患者（100%）均有血脂异常。CESD 诊断时的平均年龄为 7 岁零 2 个月。诊断依据是白细胞中缺乏 LAL 活性（所有患者）和 LIPA 基因突变（其中 47%）。所有患者均为 LIPA 基因 c.894G>A 突变的携带者。从最初症状到最终诊断大约有 3 年的延迟。
肝肿大是 CESD 最常见的临床表现。肝肿大和血脂异常定义为血清总胆固醇和 LDL 胆固醇升高、甘油三酯升高、HDL 胆固醇正常或降低，是 CESD 诊断最具特征性的发现。
