Clinical Features of Lysosomal Acid Lipase Deficiency

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; 61(6):619-25

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

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