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J Pediatr Gastroenterol Nutr. 2015 Dec;61(6):619-25. doi: 10.1097/MPG.0000000000000935.

Clinical Features of Lysosomal Acid Lipase Deficiency.

Author information

1
*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.

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).

CONCLUSION:

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01528917.

PMID:
26252914
PMCID:
PMC4645959
DOI:
10.1097/MPG.0000000000000935
[Indexed for MEDLINE]
Free PMC Article

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