title: Lysosomal acid lipase deficiency: Expanding differential diagnosis.
abstract: The differential diagnoses for metabolic liver diseases may be challenging in clinical settings, which represents a critical issue for disorders such as lysosomal acid lipase deficiency (LAL-D). LAL-D is caused by deficient activity of the LAL enzyme, resulting in the accumulation of cholesteryl esters and triglycerides throughout the body, predominately in the liver, spleen, gastrointestinal tract, and blood vessel walls. LAL-D is a progressive, multi-organ disease with early mortality and significant morbidity characterized by a combination of hepatic dysfunction and dyslipidemia. Evidence suggests LAL-D may be substantially underdiagnosed or misdiagnosed, which is critical given that disease progression can be unpredictable, with liver failure and/or accelerated atherosclerosis potentially contributing to early mortality. However, given the development of a simple diagnostic test and recently approved treatment, LAL-D should be incorporated into the differential diagnosis in relevant clinical settings. LAL-D can be diagnosed using an LAL enzyme-based biochemical test, thereby allowing for active monitoring of patients to detect potential disease complications and consider treatment options including diet, lipid-lowering medication, and treatment with sebelipase alfa, a recombinant enzyme replacement therapy shown to provide clinical benefit and improve disease-relevant markers in clinical trials. To illustrate the complexity of diagnosing LAL-D, this manuscript will describe the path to diagnosing LAL-D in a series of patient cases in which LAL-D was diagnosed as well as in patients where other diseases, such as Gaucher disease and Niemann-Pick disease, were initially suspected.
authors.affiliation: Hôpital Necker, Enfants Malades, Paris, France; Sanofi Genzyme Corporation, Cambridge, MA, USA. Electronic address: vassilival.boston@gmail.com.
authors.forename: Vassili
authors.initials: V
authors.lastname: Valayannopoulos
authors.affiliation: Villa Metabolica, Center for Pediatric and Adolescent Medicine, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Eugen
authors.initials: E
authors.lastname: Mengel
authors.affiliation: Hôpital Necker, Enfants Malades, Paris, France; Sanofi Genzyme Corporation, Cambridge, MA, USA.
authors.forename: Anais
authors.initials: A
authors.lastname: Brassier
authors.affiliation: Children's Hospital Research Foundation, Cincinnati, OH, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Grabowski
mesh_terms: D000293:Adolescent; D002648:Child; D002788:Cholesterol Esters / Q000378:metabolism; D003937:Diagnosis, Differential; D018450:Disease Progression; D042241:Early Diagnosis; D005260:Female; D005776:Gaucher Disease / Q000378:metabolism; D006801:Humans; D007223:Infant; D008297:Male; D009542:Niemann-Pick Diseases / Q000378:metabolism; D002787:Sterol Esterase / Q000378:metabolism* / Q000627:therapeutic use*; D014280:Triglycerides / Q000378:metabolism; D015223:Wolman Disease / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D002788:Cholesterol Esters; D014280:Triglycerides; C503451:LIPA protein, human; D002787:Sterol Esterase; C000603932:Sebelipase alfa
keywords: Dyslipidemia; Enzyme replacement therapy; Hepatomegaly; Lysosomal acid lipase deficiency; Lysosomal storage disease; Microvesicular steatosis