Department of Pediatric Gastroenterology, Hepatology and Nutrition, Ankara University School of Medicine, Ankara.
Department of Pediatric Gastroenterology, Hepatology and Nutrition, Ondokuz Mayıs University, School of Medicine, Samsun.
J Pediatr Gastroenterol Nutr. 2019 Mar;68(3):371-376. doi: 10.1097/MPG.0000000000002224.
Evidence suggests that lysosomal acid lipase deficiency (LAL-D) is often underdiagnosed because symptoms may be nonspecific. We aimed to investigate the prevalence of LAL-D in children with unexplained liver disease and to identify demographic and clinical features with a prospective, multicenter, cross-sectional study.
Patients (aged 3 months-18 years) who had unexplained transaminase elevation, unexplained hepatomegaly or hepatosplenomegaly, obesity-unrelated liver steatosis, biopsy-proven cryptogenic fibrosis and cirrhosis, or liver transplantation for cryptogenic cirrhosis were enrolled. A Web-based electronic data collection system was used. LAL activity (nmol/punch/h) was measured using the dried blood spot method and classified as LAL-D (<0.02), intermediate (0.02-0.37) or normal (> 0.37). A second dried blood spot sample was obtained from patients with intermediate LAL activity for confirmation of the result.
A total of 810 children (median age 5.6 years) from 795 families were enrolled. The reasons for enrollment were unexplained transaminase elevation (62%), unexplained organomegaly (45%), obesity-unrelated liver steatosis (26%), cryptogenic fibrosis and cirrhosis (6%), and liver transplantation for cryptogenic cirrhosis (<1%). LAL activity was normal in 634 (78%) and intermediate in 174 (21%) patients. LAL-D was identified in 2 siblings aged 15 and 6 years born to unrelated parents. Dyslipidemia, liver steatosis, and mild increase in aminotransferases were common features in these patients. Moreover, the 15-year-old patient showed growth failure and microvesicular steatosis, portal inflammation, and bridging fibrosis in the liver biopsy. Based on 795 families, 2 siblings in the same family were identified as LAL-D cases, making the prevalence of LAL-D in this study population, 0.1% (0.125%-0.606%). In the repeated measurement (76/174), LAL activity remained at the intermediate level in 38 patients.
Overall, the frequency of LAL-D patients in this study (0.1%) suggests that LAL-D seems to be rare even in the selected high-risk population.
有证据表明，溶酶体酸性脂肪酶缺乏症（LAL-D）常被漏诊，因为其症状可能不具有特异性。我们旨在通过前瞻性、多中心、横断面研究调查不明原因肝病患儿中 LAL-D 的患病率，并确定其具有特征性的人口统计学和临床特征。
纳入不明原因转氨酶升高、不明原因肝肿大或肝脾肿大、与肥胖无关的肝脏脂肪变性、经活检证实的隐源性纤维化和肝硬化，或因隐源性肝硬化而行肝移植的患儿（年龄 3 个月至 18 岁）。使用基于网络的电子数据采集系统。使用干血斑法测量 LAL 活性（nmol/穿孔/h），并将其分为 LAL-D（<0.02）、中间值（0.02-0.37）或正常（>0.37）。对中间值 LAL 活性的患者获得第二份干血斑样本以确认结果。
共纳入 795 个家庭的 810 例患儿（中位年龄 5.6 岁）。入组原因包括不明原因转氨酶升高（62%）、不明原因器官肿大（45%）、与肥胖无关的肝脏脂肪变性（26%）、隐源性纤维化和肝硬化（6%）以及隐源性肝硬化的肝移植（<1%）。634 例（78%）患儿的 LAL 活性正常，174 例（21%）患儿的 LAL 活性处于中间值。发现 2 例年龄分别为 15 岁和 6 岁的 LAL-D 患儿来自于无血缘关系的父母。这些患儿的共同特征是血脂异常、肝脏脂肪变性和氨基转移酶轻度升高。此外，15 岁患儿的肝脏活检显示生长发育迟缓、微泡性脂肪变性、门脉炎症和桥接纤维化。基于 795 个家庭，同一家族中的 2 名兄弟姐妹被确定为 LAL-D 病例，使该研究人群中的 LAL-D 患病率为 0.1%（0.125%-0.606%）。在重复测量（76/174）中，38 例患者的 LAL 活性仍处于中间水平。
总体而言，本研究中 LAL-D 患者的频率（0.1%）表明，即使在选定的高危人群中，LAL-D 似乎也很少见。
