Clinical Features of Lysosomal Acid Lipase Deficiency - a Longitudinal Assessment of 48 Children and Adults

Burton, B. K.; Deegan, P. B.; Enns, G. M.; Guardamagna, O.; Horslen, S.; Hovingh, G. K.; Lobritto, S. J.; Malinova, V.; McLin, V. A.; Raiman, J.; Di Rocco, M.; Santra, S.; Sharma, R.; Sykut-Cegielska, J.; Whitley, C. B.; Eckert, S.; Valayannopoulos, V.; Quinn, A. G.

J Pediatr Gastroenterol Nutr. 2015 Aug 8


OBJECTIVE: 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 aged >/=5 years, extracted historical data and obtained prospective laboratory and imaging data on living patients to develop a longitudinal dataset. RESULTS: 49 patients were enrolled; 48 had confirmed LAL D. Mean age at first symptom was 9.0 years (range 0-42); mean age at diagnosis was 15.2 years (range 1-46). Twenty-nine (60%) patients were male and 27 (56%) were < 20 years of age at time of consent/assent. Serum transaminases were elevated in most patients with 458/499 (92%) of alanine aminotransferase values and 265/448 (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 approximately 1.15 x multiple of normal (MN) and median spleen volume was approximately 2.2 x MN. Six (13%) patients had undergone a liver transplant (aged 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.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives 4.0 License, where it is permissible to download and share the work, provided it is properly cited. The work cannot be changed in any way or used commercially.

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