Lysosomal Acid Lipase Deficiency (LAL-D) in adults: Epidemiologic Multi-Center Study Underway
A multi-center, investigator-initiated epidemiologic study is underway [clinical trial: NCT01633489] aiming to determine the proportion of adults affected by late-onset lysosomal acid lipase deficiency (LAL-D) using definitive genetic testing.
LAL-D is an autosomal recessive disease caused by mutations in the Iipase gene that lead to decreased or absent enzyme activity. Lack of such activity causes lysosomal accumulation of cholesteryl ester in various organs, including the liver, spleen and adrenals, which leads to morbidity and mortality.1 Transplant hepatologistKaren L. Krok, MD,Penn State Hershey Gastroenterology and Hepatology，解释说：“在宾夕法尼亚州和宾夕法尼亚州的其他学习中心，患有cryptogenic cir肝病或非酒精性脂肪性肝炎的成年人[NASH]正在等待肝移植，将有机会对LAL-D进行测试。LAL-D的体征和症状类似于其他常见条件。但是，有10％至15％的患者没有合并症，例如肝炎，肥胖，糖尿病或酒精用来解释这种疾病。
“Although LAL-D is considered rare, [one out of every 40,000 to 300,000 patients], no large-scale study has systematically conducted genetic testing in patients with unexplained fatty liver disease. LAL-D incidence could potentially be much higher once we start to actually look for it in patients with signs and symptoms.”
For qualifying patients, testing for the LAL-D mutation will be performed by a simple blood test developed by Synageva (Athens, GA), which has sebelipase alfa, a potential enzyme replacement treatment for LAL-D, in phase 3 development. Krok notes, “Although the blood test is not yet commercially available, it has the potential to be widely used to screen for LAL-D mutations in patients with unexplained fatty liver disease.”
The current trial may help to lay the ground work for properly selecting patients for the test and interpreting its results. The availability of such a blood test may reduce the use of biopsy to investigate symptoms. Accurate diagnosis of the genetic LAL-D mutation, in turn, may help to guide more efficient management of symptoms.
LAL-D沿临床光谱呈现。新生儿病例（沃尔曼氏病）是最严重的LAL缺乏症，通常在几个月内导致死亡。许多患有LAL-D的成年人具有剩余的LAL酶活性。症状在年龄较大之前可能不会在临床上变得明显。这样的患者通常被误诊为患有非酒精性脂肪肝病或脂肪性肝炎，或隐性肝病，这是症状的治疗；患者面临的预后不佳通常导致肝衰竭和死亡。
医学博士Karen Krok
Professor of Medicine
Penn State Hershey Gastroenterology and Hepatology
Phone:717-531-6261
Email:kkrok@pennstatehealth.psu.edu
Fellowship:Transplant hepatology, gastroenterology, The Johns Hopkins Hospital, Baltimore, Md.
住院医师:Internal medicine, University of Pennsylvania Medical Center, Philadelphia, Pa.
Medical School:University of Pennsylvania School of Medicine, Philadelphia, Pa.
Connect with Karen Krok, MD, on Doximity
Reference:
- Bernstein DL, Hulkova H, Bialer MG, Desnick RJ. 2013.胆甾醇酯存储疾病:Review of the findings in 135 reported patients with an underdiagnosed disease.J Hepatol. 58:1230-1243.