Pierre Poinsot1, Sophie Collardeau Frachon2, Lioara Restier3, André Sérusclat4, Mathilde Di Filippo5, Sybil Charrière6, Philippe Moulin6, Alain Lachaux7, Noel Peretti8. 1. Univ Lyon, Hospices Civils de Lyon, Service d'Hépathologie, Gastro-entérologie et Nutrition Pédiatrique, Hopital Femme Mere Enfant, Bron, France. Electronic address: pierre.poinsot91@gmail.com. 2. Univ Lyon, Hospices Civils de Lyon, Centre de Pathologie Est, Groupement Hospitalier Est, Bron, France. 3. Univ Lyon, Hospices Civils de Lyon, Service d'Hépathologie, Gastro-entérologie et Nutrition Pédiatrique, Hopital Femme Mere Enfant, Bron, France. 4. Univ Lyon, Hospices Civils de Lyon, Service d'Imagerie Médicale, Hôpital Louis Pradel, Bron, France. 5. Univ Lyon, Hospices Civils de Lyon, Centre de Biologie Est, Groupement Hospitalier Est, Bron, France; Univ Lyon, CarMeN Laboratory, INSERM U1060, INRA U1397, Université Claude Bernard Lyon 1, INSA Lyon, Charles Merieux Medical School, Oullins, France. 6. Univ Lyon, CarMeN Laboratory, INSERM U1060, INRA U1397, Université Claude Bernard Lyon 1, INSA Lyon, Charles Merieux Medical School, Oullins, France; Univ Lyon, Hospices Civils de Lyon, Service Diabétologie, Endocrinologie, Maladies Métaboliques et Nutrition, Hôpital Louis Pradel, Bron, France; Univ Lyon, Faculté de Médecine Lyon-Est, Lyon, France. 7. Univ Lyon, Hospices Civils de Lyon, Service d'Hépathologie, Gastro-entérologie et Nutrition Pédiatrique, Hopital Femme Mere Enfant, Bron, France; Univ Lyon, Faculté de Médecine Lyon-Est, Lyon, France. 8. Univ Lyon, Hospices Civils de Lyon, Service d'Hépathologie, Gastro-entérologie et Nutrition Pédiatrique, Hopital Femme Mere Enfant, Bron, France; Univ Lyon, CarMeN Laboratory, INSERM U1060, INRA U1397, Université Claude Bernard Lyon 1, INSA Lyon, Charles Merieux Medical School, Oullins, France; Univ Lyon, Faculté de Médecine Lyon-Est, Lyon, France.
Abstract
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.
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.
Authors: Camila da Rosa Witeck; Anne Calbusch Schmitz; Júlia Meller Dias de Oliveira; André Luís Porporatti; Graziela De Luca Canto; Maria Marlene de Souza Pires Journal: J Pediatr (Rio J) Date: 2021-05-06 Impact factor: 2.990