[en] BACKGROUND: Wolman disease (WD), the rapidly progressive phenotype of lysosomal acid lipase (LAL) deficiency, presents in neonates with failure to thrive and hepatosplenomegaly, and leads to multi-organ failure and death before 12 months of age. In clinical trials, enzyme replacement therapy (ERT) with sebelipase alfa led to improved survival, growth and biological parameters in WD patients followed up to 5 years. Long-term follow-up and health-related quality of life (HRQoL) evaluation are lacking.
RESULTS: We performed a nationwide, retrospective study of sebelipase alfa in WD patients. Five patients with abolished LAL activity and bi-allelic LIPA mutations were included with a median follow-up of 7 years (1-10). ERT was initiated at a median age of 1 month (0-4). Infusion tolerance was excellent on the long-term with only one patient requiring systematic pre-medication. Cholestyramine, fat-soluble vitamin supplements and a specific diet (high in medium-chain triglycerides and low in long-chain fatty acids) were prescribed. Liver function tests, plasma lipid profiles, fat-soluble vitamin levels and growth parameters improved. Three patients transiently exhibited a neuromyopathic phenotype (footdrop gait, waddling walk or muscle fatigue) but electromyography and muscle strength testing were normal. At last follow-up, all patients were alive with normal growth parameters and a satisfactory HRQoL, no patient had special education needs, and one patient required parenteral nutrition since an acute gastroenteritis.
CONCLUSIONS: Early ERT initiation allowed 100% survival with positive outcomes. Very long-term follow-up and hematopoietic stem cell transplantation while on ERT should be evaluated to strengthen the benefits of sebelipase alfa.
Disciplines :
Pediatrics
Author, co-author :
Demaret, Tanguy ; Université de Liège - ULiège > Faculté de Médecine > Mast. spéc. gén. clin. ; Pediatric Department, Cliniques universitaires Saint-Luc, Université Catholique de Louvain (UCLouvain), Brussels, Belgium. tanguy.demaret@ipg.be ; Centre for Human Genetics, Institut de Pathologie et de Génétique, Gosselies, Belgium. tanguy.demaret@ipg.be
Lacaille, Florence ; Gastroenterology-Hepatology-Nutrition Unit, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris (APHP), Université de Paris, Paris, France
Wicker, Camille; Reference Center for Inherited Metabolic Diseases, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris (APHP), Institut Imagine, Université de Paris, 149 Rue de Sèvres, 75015, Paris, France
Arnoux, Jean-Baptiste ; Reference Center for Inherited Metabolic Diseases, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris (APHP), Institut Imagine, Université de Paris, 149 Rue de Sèvres, 75015, Paris, France
Bouchereau, Juliette ; Reference Center for Inherited Metabolic Diseases, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris (APHP), Institut Imagine, Université de Paris, 149 Rue de Sèvres, 75015, Paris, France
Belloche, Claire; Reference Center for Inherited Metabolic Diseases, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris (APHP), Institut Imagine, Université de Paris, 149 Rue de Sèvres, 75015, Paris, France
Gitiaux, Cyril ; Paediatric Neurophysiology Department and Reference Center for Neuromuscular Diseases, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris (APHP), Université de Paris, Paris, France
Grevent, David ; Paediatric Radiology Department, Hôpital Necker Enfants Malades, Assistance Publique Hôpitaux de Paris (APHP), Université de Paris, Paris, France
Broissand, Christine; Pharmacy Department, Hôpital Necker Enfants Malades, Assistance Publique Hôpitaux de Paris (APHP), Université de Paris, Paris, France
Adjaoud, Dalila; Pediatric Oncology and Hematology Department, CHU Grenoble Alpes, Grenoble, France
Abi Warde, Marie-Thérèse; Pediatric Neurology Department, CHU de Strasbourg, Strabourg, France
Plantaz, Dominique; Pediatric Oncology and Hematology Department, CHU Grenoble Alpes, Grenoble, France
Bekri, Soumeya ; Metabolic Biochemistry Department, CHU de Rouen, INSERM U1245, Université de Rouen Normandie, Rouen, France
de Lonlay, Pascale ; Reference Center for Inherited Metabolic Diseases, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris (APHP), Institut Imagine, Université de Paris, 149 Rue de Sèvres, 75015, Paris, France
Brassier, Anaïs; Reference Center for Inherited Metabolic Diseases, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris (APHP), Institut Imagine, Université de Paris, 149 Rue de Sèvres, 75015, Paris, France. anais.brassier@aphp.fr
The authors thank Eric Bauchart for the help provided with the data collection. TD acknowledges Prof. Etienne Sokal for the freedom and the?strong support he provided him to learn metabolic disease management during his PhD.
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