Clinical Features of Lysosomal Acid Lipase Deficiency

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


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: NCT01528917.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alanine Transaminase / blood
  • Aspartate Aminotransferases / blood
  • Child
  • Child, Preschool
  • Cholesterol / blood*
  • Cholesterol Ester Storage Disease* / blood
  • Cholesterol Ester Storage Disease* / pathology
  • Fatty Liver / blood
  • Fatty Liver / etiology*
  • Female
  • Humans
  • Lipase / deficiency
  • Liver Cirrhosis / etiology
  • Liver Transplantation
  • Liver* / metabolism
  • Liver* / pathology
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Prospective Studies
  • Spleen / pathology
  • Sterol Esterase / deficiency*
  • Wolman Disease* / blood
  • Wolman Disease* / pathology
  • Young Adult


  • Cholesterol
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Sterol Esterase
  • Lipase

Supplementary concepts

  • Lysosomal acid lipase deficiency

Associated data