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 approximate to 1.15 multiples of normal (MN) and median spleen volume was approximate to 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.