Tebani Abdellah, Sudrié-Arnaud Bénédicte, Boudabous Hela, Brassier Anais, Anty Rodolphe, Snanoudj Sarah, Abergel Armand, Abi Warde Marie-Thérèse, Bardou-Jacquet Edouard, Belbouab Reda, Blanchet Eloi, Borderon Corinne, Bronowicki Jean-Pierre, Cariou Bertrand, Carette Claire, Dabbas Myriam, Dranguet Hélène, de Ledinghen Victor, Ferrières Jean, Guillaume Maeva, Krempf Michel, Lacaille Florence, Larrey Dominique, Leroy Vincent, Musikas Marietta, Nguyen-Khac Eric, Ouzan Denis, Perarnau Jean-Marc, Pilon Carine, Ratzlu Vlad, Thebaut Alice, Thevenot Thierry, Tragin Isabelle, Triolo Valérie, Vergès Bruno, Vergnaud Sabrina, Bekri Soumeya
Normandie Univ, UNIROUEN, INSERM U1245, CHU Rouen, Department of Metabolic Biochemistry, 76000 Rouen, France.
Pediatric Department, La Rabta Hospital, Faculty of Medecine of Tunis, University of Tunis El Manar, Jabberi, Jebal Lakhdhar, Tunis, Tunisia.
Clin Chim Acta. 2021 Aug;519:64-69. doi: 10.1016/j.cca.2021.04.005. Epub 2021 Apr 20.
Lysosomal acid lipase deficiency (LALD, OMIM#278000) is a rare lysosomal disorder with an autosomal recessive inheritance. The main clinical manifestations are related to a progressive accumulation of cholesteryl esters, triglycerides or both within the lysosome in different organs such as the liver, spleen, and cardiovascular system. A wide range of clinical severity is associated with LALD including a severe very rare antenatal/neonatal/infantile phenotype named Wolman disease and a late-onset form named cholesteryl ester storage disease (CESD).
This study aimed to investigate a cohort of at-risk patients (4174) presenting with clinical or biological signs consistent with LALD using the assessment of LAL activity on dried blood spots.
LAL activity was lower than 0.05 nmol/punch/L (cut-off: 0.12) in 19 patients including 13 CESD and 6 Wolman. Molecular study has been conducted in 17 patients and succeeded in identifying 34 mutated alleles. Fourteen unique variants have been characterized, 7 of which are novel.
This study allowed to identify a series of patients and expanded the molecular spectrum knowledge of LALD. Besides, a new screening criteria grid based on the clinical/biological data from our study and the literature has been proposed in order to enhance the diagnosis rate in at risk populations.
溶酶体酸性脂肪酶缺乏症（LALD，OMIM#278000）是一种罕见的溶酶体疾病，呈常染色体隐性遗传。主要临床表现与胆固醇酯、甘油三酯或两者在肝脏、脾脏和心血管系统等不同器官的溶酶体内进行性蓄积有关。LALD具有广泛的临床严重程度，包括一种严重的极罕见的产前/新生儿/婴儿期表型，即沃尔曼病，以及一种迟发型，即胆固醇酯贮积病（CESD）。
本研究旨在通过评估干血斑中的LAL活性，调查一组有LALD临床或生物学体征的高危患者（4174例）。
19例患者的LAL活性低于0.05 nmol/打孔/L（临界值：0.12），其中包括13例CESD和6例沃尔曼病患者。对17例患者进行了分子研究，成功鉴定出34个突变等位基因。已鉴定出14个独特的变异体，其中7个是新发现的。
本研究识别出了一系列患者，扩展了对LALD分子谱的认识。此外，基于本研究及文献中的临床/生物学数据，提出了一个新的筛查标准网格，以提高高危人群的诊断率。
