Ace the Case: A 28-Year-Old Man With Hepatomegaly and Dyslipidemia

Summary and References


LAL-D is a rare genetic disease with significant morbidity and early mortality due to the marked decrease of LAL enzyme activity, which results in the accumulation of lipid substrates in various tissues and cell types, and the complex dyslipidemia that subsequently results, increasing the risk of cardiovascular disease.2

There is a need for enhanced awareness of LAL-D so that early diagnosis can help limit disease-associated morbidity and mortality. Differential diagnosis is key because a number of other conditions have similar clinical and laboratory presentations. Early recognition and diagnosis of individuals with LAL-D is essential if appropriate care is to be provided. The recent development of a blood test for LAL-D1 provides physicians with a method for rapid diagnosis, and FDA approval of sebelipase offers a therapeutic option for this rare but devastating disease.11


  1. Hamilton J, et al. A new method for the measurement of lysosomal acid lipase in dried blood spots using the inhibitor Lalistat 2. Clin Chim Acta. 2012;413(15-16):1207-1210.
  2. Scott SA, et al. Frequency of the cholesteryl ester storage disease common LIPA E8SJM mutation (c.894G>A) in various racial and ethnic groups. Hepatology. 2013;58:958-965.
  3. Reiner Z, et al. Lysosomal acid lipase deficiency: an under-recognized cause of dyslipidemia and liver dysfunction. Atherosclerosis. 2014;235(1):21-30.
  4. Zhang B, et al. Cholesteryl ester storage disease: protean presentations of lysosomal acid lipase deficiency. J Pediatr Gastroenterol Nutr. 2013;56(6):682-5.
  5. Burton BK, et al. Clinical Features of Lysosomal Acid Lipase Deficiency. J Pediatr Gastroenterol Nutr. 2015;61(6):619-25. 
  6. Freudenberg F, et al. Cholesteryl ester storage disease: an easily missed diagnosis in oligosymptomatic children. Z Gastroenterol. 2013;51(10):1184-1187.
  7. Saito S, et al. Structural bases of Wolman disease and cholesteryl ester storage disease. Mol Genet Metab. 2012;105(2):244-8. doi: 10.1016/j.ymgme.2011.11.004.
  8. Bernstein DL, et al. Cholesteryl ester storage disease: review of the findings in 135 reported patients with an underdiagnosed disease. J Hepatol. 2013;58(6):1230-1243.
  9. Reynolds T. Cholesteryl ester storage disease: a rare and possibly treatable cause of premature vascular disease and cirrhosis. J Clin Pathol. 2013;66:918-923.
  10. Valayannopoulos V, et al. Sebelipase alfa over 52 weeks reduces serum transaminases, liver volume and improves serum lipids in patients with lysosomal acid lipase deficiency. J Hepatol. 2014;61(5):1135-1142.
  11. Actelion Pharmaceuticals. December 8, 2015. FDA Approves Kanuma™ (sebelipase alfa) for the Treatment of Patients with Lysosomal Acid Lipase Deficiency (LAL-D)., 2019.