Childhood/adult-onset lysosomal acid lipase deficiency: A serious metabolic and vascular phenotype beyond liver disease—four new pediatric cases

• Published in: Journal of clinical lipidology 2017-01, Vol.11 (1), p.167-177.e3
• Main Authors: Poinsot, Pierre, MD, Collardeau Frachon, Sophie, MD, PhD, Restier, Lioara, PhD, Sérusclat, André, MD, Di Filippo, Mathilde, MD, PhD, Charrière, Sybil, MD, PhD, Moulin, Philippe, MD, PhD, Lachaux, Alain, MD, PhD, Peretti, Noel, MD, PhD
• Format: Article
• Language: English
• Subjects: Adolescent; Atherosclerosis; Atherosclerosis - complications; Cardiovascular; Child; Childhood/adult-onset LALD; Children non-alcoholic fatty liver disease; Cholesterol ester storage disease; Dyslipidemia; Female; Genetic hepatic steatosis; Humans; Hypercholesterolemia; Infant, Newborn; Insulin resistance; Intima-media thickness; Life Sciences; Liver Diseases - complications; Male; Middle Aged; Mutation; Phenotype; Sterol Esterase - genetics; Sterol Esterase - metabolism; Wolman Disease; Wolman Disease - complications; Wolman Disease - diagnosis; Wolman Disease - genetics; Wolman Disease - metabolism
• ISSN: 1933-2874; 1876-4789
• DOI: 10.1016/j.jacl.2016.11.008

Background The childhood/adult-onset lysosomal acid lipase deficiency (LALD; late-onset LALD) is a rare genetic disease. Children present severe fatty liver disease with early cirrhosis. Before enzyme replacement therapy, statins were the standard treatment to improve the severe dyslipidemia. However, late-onset LALD should be considered as a systemic metabolic disease: chronic hyper-low-density lipoprotein and hypo-high-density lipoprotein cholesterolemia induces early atherosclerosis in addition to the liver morbidity. Objective To assess 4 new pediatric cases of late-onset LALD with an evaluation of hepatic, metabolic, and vascular evolution under statin. Methods Four patients were retrospectively described. Anthropometric data (weight, height, and body mass index) and laboratory data ( LIPA mutations, acid lipase residual activity, liver and lipid profile, and homeostatic model assessment index) were collected. Liver histology was assessed by the noninvasive tests FibroScan and FibroTest and confirmed by liver biopsy. Vascular impact was followed up by carotid intima-media thickness (cIMT) assessment. Results The 4 cases of late-onset LALD came from 2 families, each with a boy (aged 8.6 and 11 years at diagnosis) and a girl (aged 10.6 and 13 years at diagnosis). Treatment with statins was performed for 8 and 5 years, respectively, from diagnosis. Statins decreased the low-density lipoprotein cholesterol mean value of 40%. All children showed significant liver fibrosis (F3 [n = 3]; F2 [n = 1]). cIMT showed the following for all children: abnormal measures without improvement and atherosclerotic plaques. One child developed a deleterious metabolic phenotype with obesity and insulin resistance (homeostatic model assessment = 3.08) associated with higher mean hepatic transaminases (149 vs 98, 88, and 61 IU/L) and increased mean cIMT values (raising from 0.47 to 0.5 mm vs 0.43 and 0.43 mm). Conclusion Late-onset LALD is a rare metabolic disease with a larger impact than liver disease. Our work shows the importance of having a global metabolic view and to evaluate the cardiovascular impact of the new enzymatic treatment.