Tylki-Szymańska Anna, Jurecka Agnieszka
Department of Pediatrics, Nutrition and Metabolic Diseases, The Children's Memorial Health Institute, Warsaw, Poland.
Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.
Pril (Makedon Akad Nauk Umet Odd Med Nauki). 2014;35(1):99-106.
Cholesteryl ester storage disease (CESD, OMIM #278000) and Wolman disease (OMIM #278000) are autosomal recessive lysosomal storage disorders caused by a deficient activity of lysosomal acid lipase (cholesteryl ester hydrolase, LAL). Human lysosomal acid lipase is essential for the metabolism of cholesteryl esters and triglycerides. In Wolman disease, LAL activity is usually absent, whereas CESD usually presents some residual LAL activity. In infants, poor weight gain, massive hepatosplenomegaly, calcified adrenal glands (present about 2/3 of the time), vomiting, diarrhea and failure to thrive are indicative of Wolman disease. The clinical picture is more variable in CESD. Hepatomegaly and/or elevation of liver transaminases are almost always present. Hepatic steatosis often leads to fibrosis and cirrhosis. Other signs often include splenomegaly, high total cholesterol and LDL-cholesterol, elevated triglycerides, and low HDL-cholesterol. The diagnosis of LAL deficiency requires clinical experience and specialized laboratory tests. The diagnosis is based on finding deficient activity of acid lipase and/or molecular tests. Pilot screening projects using dried blood spot testing in 1) children with atypical fatty liver disease in the absence of overweight, 2) patients with dyslipidaemia and presence of hepatomegaly and/or elevated transaminases, 3) newborns/neonates with hepatomegaly and abdominal distension/failure to thrive/elevated transaminases are currently underway. Early diagnosis is particularly important for the enzyme replacement therapy. Human trials with recombinant LAL are currently ongoing, raising the prospect for specific correction of LAL deficiency in this progressive and often debilitating disorder.
胆固醇酯贮积病（CESD，OMIM #278000）和沃尔曼病（OMIM #278000）是常染色体隐性溶酶体贮积症，由溶酶体酸性脂肪酶（胆固醇酯水解酶，LAL）活性不足引起。人类溶酶体酸性脂肪酶对胆固醇酯和甘油三酯的代谢至关重要。在沃尔曼病中，通常不存在LAL活性，而CESD通常存在一些残余的LAL活性。在婴儿中，体重增加不佳、肝脾肿大、肾上腺钙化（约2/3的情况出现）、呕吐、腹泻和发育不良是沃尔曼病的指征。CESD的临床表现则更为多样。肝肿大和/或肝转氨酶升高几乎总是存在。肝脂肪变性常导致纤维化和肝硬化。其他体征通常包括脾肿大、总胆固醇和低密度脂蛋白胆固醇升高、甘油三酯升高以及高密度脂蛋白胆固醇降低。LAL缺乏症的诊断需要临床经验和专门的实验室检查。诊断基于发现酸性脂肪酶活性不足和/或分子检测。目前正在进行试点筛查项目，使用干血斑检测来筛查以下人群：1）无超重的非典型脂肪肝患儿；2）患有血脂异常且存在肝肿大和/或转氨酶升高的患者；3）患有肝肿大和腹胀/发育不良/转氨酶升高的新生儿/婴儿。早期诊断对于酶替代疗法尤为重要。目前正在进行重组LAL的人体试验，这为这种进行性且往往使人衰弱的疾病中LAL缺乏症的特异性纠正带来了希望。
