Deficiency of Lysosomic Acid Lipase: Clinical Recommendations for Child Health Care Delivery

The deficiency of lysosomic acid lipase is a rare hereditary enzymopathy. The focus of this article is the present condition of this issue. The authors demonstrate epidemiological data and etiopathogenetic features of two phenotypic forms of lysosomic acid lipase deficiency — Wolman disease and cholesterol ester storage disease. Clinical features of both — the rapidly progressing form and the slowly developing cholesterol ester storage disease — are described in detail in this article. The algorithm and crucial steps of differential diagnosis are described in detail. Also, indications to pathogenetic therapy are carefully formulated, and the tactic of enzyme replacing therapy is given. The modern approaches to the management of child patients are described.

1. Bernstein DL, Hulkova H, Bialer MG, Desnick RJ. Cholesteryl ester storage disease: review of the findings in 135 reported patients with an underdiagnosed disease. J Hepatol. 2013;58:1230–43.

2. Fouchier SW, Defesche JC. Lysosomal acid lipase A and the hyper cholesterolaemic phenotype. Curr Opin Lipidol. 2013; 24:332–8.

3. Hulkova H, Elleder M. Distinctive histopathological features that support a diagnosis of cholesterol ester storage disease in liver biopsy specimens. Histopathology. 2012;60:1107e13.

4. Grabowski GA, Charnas L, Du H. Lysosomal acid lipase deficiencies: the Wolman disease/cholesteryl ester storage disease spectrum. In: Scriver Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, editors. Metabolic and molecular bases of inherited disease, OMMBID. New York: McGraw-Hill; 2012.

5. Hamilton J, Jones I, Srivastava R, Galloway P. A new method for the measurement of lysosomal acid lipase in dried blood spots using the inhibitor Lalistat 2. Clin Chim Acta. 2012;413:1207e10.

6. Quinn AG, Burton B, Deegan P, Di Rocco M, Enns GM, Guardamagna O, et al. Sustained elevations in LDL cholesterol and serum transaminases from early childhood are common in lysosomal acid lipase deficiency. Mol Genet Metab. 2014;111:S89.

7. Ambler GK, Hoare M, Brais R, Shaw A, Butler A, Flynn P, et al. Orthotopic liver transplantation in an adult with cholesterol ester storage disease. JIMD Rep. 2013;8:41–6.

8. Abello F, Guardamagna O, Baracco V, Bonardi R. The treatment of colesteryl storage disease (CESD) by ezetimibe monotherapy. Atheroscler Suppl. 2010;11:28.

9. Xu M, Liu K, Swaroop M, Porter FD, Sidhu R, Firnkes S, et al. 5-Tocopherol reduces lipid accumulation in Niemann-Pick type C1 and Wolman cholesterol storage disorders. J Biol Chem. 2012;287:39349–60.

10. Barton BK, Balwani M, Feillet F. A phase 3 trial of sebelipase alfa in lysosomal acid lipase deficiency. N Engl J Med. 2015;373(11):1010–1020.