title: Clinical Features of Lysosomal Acid Lipase Deficiency.
abstract: OBJECTIVE
  The aim of this study was to characterize key clinical manifestations of lysosomal acid lipase deficiency (LAL D) in children and adults.
  
  
  METHODS
  Investigators reviewed medical records of LAL D patients ages ≥5 years, extracted historical data, and obtained prospective laboratory and imaging data on living patients to develop a longitudinal dataset.
  
  
  RESULTS
  A total of 49 patients were enrolled; 48 had confirmed LAL D. Mean age at first disease-related abnormality was 9.0 years (range 0-42); mean age at diagnosis was 15.2 years (range 1-46). Twenty-nine (60%) were male patients, and 27 (56%) were <20 years of age at the time of consent/assent. Serum transaminases were elevated in most patients with 458 of 499 (92%) of alanine aminotransferase values and 265 of 448 (59%) of aspartate aminotransferase values above the upper limit of normal. Most patients had elevated low-density lipoprotein (64% patients) and total cholesterol (63%) at baseline despite most being on lipid-lowering therapies, and 44% had high-density lipoprotein levels below the lower limit of normal. More than half of the patients with liver biopsies (n = 31, mean age 13 years) had documented evidence of steatosis (87%) and/or fibrosis (52%). Imaging assessments revealed that the median liver volume was ∼1.15 multiples of normal (MN) and median spleen volume was ∼2.2 MN. Six (13%) patients had undergone a liver transplant (ages 9-43.5 years).
  
  
  CONCLUSIONS
  This study provides the largest longitudinal case review of patients with LAL D and confirms that LAL D is predominantly a pediatric disease causing early and progressive hepatic dysfunction associated with dyslipidemia that often leads to liver failure and transplantation.
authors.affiliation: *Division of Genetics, Birth Defects and Metabolism, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL †Department of Medicine, Addenbrooke's Hospital NHS Trust, Cambridge, UK ‡Medical Genetics Division, Stanford University, Stanford, CA §Department of Pediatrics, Regina Margherita Hospital, Turin, Italy ||Seattle Children's Hospital, Seattle, WA ¶Department of Vascular Medicine-Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands #New York-Presbyterian/Columbia University Medical Center, New York, NY **Department of Pediatrics, First Faculty of Medicine, Charles University, Prague, Czech Republic ††Departement de l'Enfant et de l'Adolescent, Hopitaux Universitaires de Geneve, Geneva, Switzerland ‡‡Division of Clinical and Metabolic Genetics, Hospital for Sick Children, Toronto, Ontario, Canada §§Department of Pediatrics, Unit of Rare Diseases, Gaslini Institute Genoa, Genova, Italy ||||Department of Inherited Metabolic Disorders, Birmingham Children's Hospital, Birmingham, UK ¶¶Department of Adult Inherited Metabolic Diseases, Salford Royal NHS Foundation, Salford, UK ##Screening Department, Institute of Mother and Child, Warsaw, Poland ***University of Minnesota, Minneapolis, MN †††Synageva BioPharma Corp, Lexington, MA ‡‡‡Hopital Necker-Enfants Malades, Paris, France.
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Burton
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Deegan
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Enns
authors.forename: Ornella
authors.initials: O
authors.lastname: Guardamagna
authors.forename: Simon
authors.initials: S
authors.lastname: Horslen
authors.forename: Gerard K
authors.initials: GK
authors.lastname: Hovingh
authors.forename: Steve J
authors.initials: SJ
authors.lastname: Lobritto
authors.forename: Vera
authors.initials: V
authors.lastname: Malinova
authors.forename: Valerie A
authors.initials: VA
authors.lastname: McLin
authors.forename: Julian
authors.initials: J
authors.lastname: Raiman
authors.forename: Maja
authors.initials: M
authors.lastname: Di Rocco
authors.forename: Saikat
authors.initials: S
authors.lastname: Santra
authors.forename: Reena
authors.initials: R
authors.lastname: Sharma
authors.forename: Jolanta
authors.initials: J
authors.lastname: Sykut-Cegielska
authors.forename: Chester B
authors.initials: CB
authors.lastname: Whitley
authors.forename: Stephen
authors.initials: S
authors.lastname: Eckert
authors.forename: Vassili
authors.initials: V
authors.lastname: Valayannopoulos
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Quinn
mesh_terms: D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000097:blood*; D015217:Cholesterol Ester Storage Disease / Q000097:blood / Q000473:pathology; D005234:Fatty Liver / Q000097:blood / Q000209:etiology*; D005260:Female; D006801:Humans; D008049:Lipase / Q000172:deficiency; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000209:etiology; D016031:Liver Transplantation; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013154:Spleen / Q000473:pathology; D002787:Sterol Esterase / Q000172:deficiency*; D015223:Wolman Disease / Q000097:blood / Q000473:pathology; D055815:Young Adult
chemical_list: D002784:Cholesterol; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D002787:Sterol Esterase; D008049:Lipase