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Managing Cardiovascular Risk in Lysosomal Acid Lipase Deficiency

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An Erratum to this article was published on 25 March 2017

Abstract

Lysosomal acid lipase deficiency (LAL-D) is a rare, life-threatening, autosomal recessive, lysosomal storage disease caused by mutations in the LIPA gene, which encodes for lysosomal acid lipase (LAL). This enzyme is necessary for the hydrolysis of cholesteryl ester and triglyceride in lysosomes. Deficient LAL activity causes accumulation of these lipids in lysosomes and a marked decrease in the cytoplasmic free cholesterol concentration, leading to dysfunctional cholesterol homeostasis. The accumulation of neutral lipid occurs predominantly in liver, spleen, and macrophages throughout the body, and the aberrant cholesterol homeostasis causes a marked dyslipidemia. LAL-D is characterized by accelerated atherosclerotic cardiovascular disease (ASCVD) and hepatic microvesicular or mixed steatosis, leading to inflammation, fibrosis, cirrhosis and liver failure. LAL-D presents as a clinical continuum with two phenotypes: the infantile-onset phenotype, formally referred to as Wolman disease, and the later-onset phenotype, formerly referred to as cholesteryl ester storage disease. Infants with LAL-D present within the first few weeks of life with vomiting, diarrhea, hepatosplenomegaly, failure to thrive and rapid progression to liver failure and death by 6–12 months of age. Children and young adults with LAL-D generally present with marked dyslipidemia, hepatic enzyme elevation, hepatomegaly and mixed steatosis by liver biopsy. The average age of the initial signs and symptoms of the later-onset phenotype is about 5 years old. The typical dyslipidemia is a significantly elevated low-density lipoprotein cholesterol (LDL-C) concentration and a low high-density lipoprotein cholesterol (HDL-C) concentration, placing these individuals at heightened risk for premature ASCVD. Diagnosis of the later-onset phenotype of LAL-D requires a heightened awareness of the disease because the dyslipidemia and hepatic transaminase elevation combination are common and overlap with other metabolic disorders. LAL-D should be considered in the differential diagnosis of healthy weight children and young adults with unexplained hepatic transaminase elevation accompanied by an elevated LDL-C level (>160 mg/dL) and low HDL-C level (<35 mg/dL) that is not caused by monogenic and polygenic lipid disorders or secondary factors. Treatment of LAL-D with sebelipase alfa (LAL replacement enzyme) should be considered as the standard of treatment in all individuals diagnosed with LAL-D. Other ASCVD risk factors that may be present (hypertension, tobacco use, diabetes mellitus, etc.) should be managed appropriately, consistent with secondary prevention goals.

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References

  1. Grabowski GA, Du H, Charnas L. Lysosomal acid lipase deficiencies: the Wolman disease/cholesteryl ester storage disease spectrum. In: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, editors. The online metabolic and molecular basis of inherited disease. 8th ed. New York: McGraw-Hill; 2012 (Chapter 142).

    Google Scholar 

  2. Klein AD. Futerman AH Lysosomal storage disorders: old diseases present and future challenges. Ped Endocrinol Rev. 2013;11:59–63.

    Google Scholar 

  3. 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.

    Article  CAS  PubMed  Google Scholar 

  4. Goldstein JL, Dana SE, Faust JR, Beaudet AL, Brown MS. Role of lysosomal acid lipase in the metabolism of plasma low density lipoprotein. Observations in cultured fibroblasts from a patient with cholesteryl ester storage disease. J Biol Chem. 1975;250:8487–95.

    CAS  PubMed  Google Scholar 

  5. Horton JD, Goldstein JL, Brown MS. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest. 2002;109:1125–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Burton BK, Deegan PB, Enns GM, Guardamagna O, Horslen S, Hovingh GK, Lobritto SJ, Malinova V, McLin VA, Raiman J, Di Rocco M, Santra S, Sharma R, Sykut-Cegielska J, Whitley CB, Eckert S, Valayannopoulos V, Quinn AG. Clinical features of lysosomal acid lipase deficiency. J Pediatr Gastroenerol Nutr. 2015;61:619–25.

    Article  CAS  Google Scholar 

  7. Muntoni S, Wiebusch H, Jansen-Rust M, Rust S, Seedorf U, Schulte H, Berger K, Funke H, Assman G. Prevalence of cholesteryl ester storage disease. Arterioscler Thromb Vasc Biol. 2007;27:1866–8.

    Article  CAS  PubMed  Google Scholar 

  8. Stitziel NO, Fouchier SW, Sjouke B, Peloso GM, Moscoso AM, Auer PL, Goel A, Gigante B, Barnes TA, Melander O, Orho-Melander M, Duga S, Sivapalaratnam S, Nikpay M, Martinelli N, Girelli D, Jackson RD, Kooperberg C, Lange LA, Ardissino D, McPherson R, Farrall M, Watkins H, Reilly MP, Rader DJ, de Faire U, Schunkert H, Erdmann J, Samani NJ, Charnas L, Altshuler D, Gabriel S, Kastelein JJP, Defesche JC, Nederveen AJ, Kathiresan S, Hovingh GK. Exome sequencing and directed phenotyping diagnose cholesterol ester storage disease presenting as autosomal recessive hypercholesterolemia. Arterioscler Thromb Vasc Biol. 2013;33:2909–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Reiner Z, Guardamagna O, Nair D, Soran H, Hovingh K, Bertolini S, Jones S, Coric M, Calandra S, Hamilton J, Eagleton T, Ros E. Lysosomal acid lipase deficiency- an under-recognized cause of dyslipidemia and liver dysfunction. Arterioscler. 2014;235:21–30.

    Article  CAS  Google Scholar 

  10. Aslanidis C, Reis S, Fehinger P, Buchler C, Klima H, Schmitz G. Genetic and biochemical evidence that CESD and Wolman disease are distinguished by residual lysosomal acid lipase activity. Genomics. 1996;33:85–93.

    Article  CAS  PubMed  Google Scholar 

  11. Ameis D, Greten H. Lysosomal acid lipase: a pivotal enzyme in the pathogenesis of cholesteryl ester storage disease and Wolman disease. Z Gastroenterol. 1996;34(Suppl 3):66–7.

    CAS  PubMed  Google Scholar 

  12. Abramov A, Schorr S, Wolman M. Generalized xanthomatosis with calcified adrenals. Amer J Dis Child. 1956;91:282–6.

    CAS  Google Scholar 

  13. Wolman M, Sterk VV, Gatt S, Frenkel M. Primary familial xanthomatosis with involvement and calcification of the adrenals. Report of two more cases in siblings of a previously described infant. Pediatrics. 1961;28:742–57.

    CAS  PubMed  Google Scholar 

  14. Marshal WC, Ockenden BG, Fosbrooke AS, Cumings JN. Wolman’s disease. A rare lipidosis with adrenal calcification. Arch Dis Child. 1969;44:331–41.

    Article  Google Scholar 

  15. Crocker AC, Vawter GF, Neuhauser EB, Rosowsky A. Wolman’s disease: three new patients with a recently described lipidosis. Pediatrics. 1965;35:627–40.

    CAS  PubMed  Google Scholar 

  16. Schaub J, Janka GE, Christmanou H, Sandhoff K, Permanetter W, Hubner G, Meister P. Wolman’s disease: clinical, biochemical and ultrastructural studies in an unusual case without striking adrenal calcification. Eur J Pediatr. 1980;135:45–50.

    Article  CAS  PubMed  Google Scholar 

  17. Ries S, Aslannidis C, Fehinger P, Carel J-C, Gendrel D, Schmitz G. A new mutation in the gene for lysosomal acid lipase leads to Wolman disease in an African kindred. J Lipid Res. 1996;37:1761–5.

    CAS  PubMed  Google Scholar 

  18. Jones SA, Valayannopoulos V, Schneider E, Eckert S, Bankikazemi M, Bialer M, Cederbaum S, Chan A, Dhawan A, Di Rocco M, Domm J, Enns GM, Finegold D, Gargus JJ, Guardamagna O, Hendriksz C, Mahmoud IG, Raiman J, Selim LA, Whitley CB, Zaki O, Quinn AG. Rapid progression and mortality of lysosomal acid lipase deficiency presenting in infants. Genet Med. 2015. www.nature/gim (advanced online publication).

  19. Frederickson DS. Newly recognized disorders of cholesterol metabolism. Ann Intern Med. 1963;58:718.

    Article  Google Scholar 

  20. Pisciotta L, Fresa R, Bellocchio A, Pino E, Guido V, Cantafora A, Di Rocco M, Calandra S, Bertolini S. Cholesteryl ester storage disease (CESD) due to novel mutations in the LIPA gene. Mol Genet Metab. 2009;97:143–8.

    Article  CAS  PubMed  Google Scholar 

  21. Seedorf U, Wiebusch H, Muntoni S, Christensen NC, Skovby F, Nickel V, Roskos M, Funke H, Ose L, Assman G. A novel variant of lysosomal acid lipase (Leu336->Pro) associated with acid lipase deficiency and cholesterol ester storage disease. Arterioscler Thromb Vasc Biol. 1995;15:773–8.

    Article  CAS  PubMed  Google Scholar 

  22. Sheriff S, Du H, Grabowski GA. Characterization of lysosomal acid lipase by site-directed mutagenesis and heterologous expression. J Biol Chem. 1995;270:27766–277772.

    Article  CAS  PubMed  Google Scholar 

  23. Saito S, Ohno K, Suzuki H. Structural bases of Wolman disease and cholesteryl ester storage disease. Mol Genet Metab. 2012;105:244–8.

    Article  CAS  PubMed  Google Scholar 

  24. Klima H, Ullrich K, Aslanidis C, Fehringer P, Lackner KJ, Schmitz G. A splice junction mutation causes deletion of a 72-base exon from the mRNA for lysosomal acid lipase in a patient with cholesteryl ester storage disease. J Clin Invest. 1993;92:2713–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Aslanidis C, Klima H, Lackner KJ, Schmitz G. Genomic organization of human lysosomal acid lipase gene (LIPA). Genomics. 1994;20:329–31.

    Article  CAS  PubMed  Google Scholar 

  26. Koch G, Lalley PA, McAvoy M, Shows TB. Assignment of LIPA, associated with human acid lipase deficiency, to human chromosome 10 and comparative assignment to mouse chromosome 19. Somatic Cell Genet. 1981;7:345–58.

    Article  CAS  PubMed  Google Scholar 

  27. Stenson PD, Mort M, Ball EV, Howells K, Phillips AD, Thomas NS, Cooper DN. The human gene mutation database: 2008 update. Genome Med. 2009;1(1):13.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Scott SA, Liu B, Nazarenko I, Martis S, Kozlitina J, Yao Y, Ramirez C, Kasai Y, Hyatt T, Inga P, Desnick RJ. Frequency of the cholesteryl ester storage disease common LIPA E8SJM mutation (c.894G>A) in various racial and ethnic groups. Hepatology. 2013;58:958–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Pagani F, Pariyarath R, Garcia R, Stuani C, Burlina AB, Ruotolo G, Rabusin M, Baralle FE. New lysosomal acid lipase gene mutants explain the phenotype of Wolman disease and cholesteryl ester storage disease. J Lipid Res. 1998;39:1382–8.

    CAS  PubMed  Google Scholar 

  30. Ameis D, Brockman G, Knoblich R, Merkal M, Ostlund RE, Yang JW, Coates PM, Cortner JA, Feinman SV, Greten H. A 5′ splice-region mutation and a dinucleotide deletion in the lysosomal acid lipase gene in two patients with cholesteryl ester storage disease. J Lipid Res. 1995;36:241–50.

    CAS  PubMed  Google Scholar 

  31. Lohse P, Maas S, Lohse P, Elleder M, Kirk JM, Besley GT, Seidel D. Compound heterozygosity for a Wolman mutation is frequent among patients with cholesteryl ester storage disease. J Lipid Res. 2000;41:23–31.

    CAS  PubMed  Google Scholar 

  32. Peterson AS, Fong LG, Young SG. PCSK9 function and physiology. J Lipid Res. 2008;49:1303–11.

    Article  Google Scholar 

  33. Bowden KL, Bilbey NJ, Bilawchuk LM, Boadu E, Sidhu R, Ory DS, Du H, Chan T, Francis GA. Lysosomal acid lipase deficiency impairs regulation of ABCA1 gene and formation of high density lipoproteins in cholesteryl ester storage disease. J Biol Chem. 2011;286:30624–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Brown MS, Dana SE, Goldstein JL. Receptor-dependent hydrolysis of cholesteryl esters contained in plasma low density lipoprotein. Proc Natl Acad Sci USA. 1975;72:2925–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Ginsberg HN, Le NA, Short MP, Ramakrishnan R, Desnick RJ. Suppression of apolipoprotein B production during treatment of cholesteryl ester storage disease with lovastatin. Implications for regulation of apolipoprotein B synthesis. J Clin Invest. 1987;80:1692–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Cummings MH, Watts GF. Increased hepatic secretion of very-low-density lipoprotein apolipoprotein B-100 in cholesteryl ester storage disease. Clin Chem. 1995;41:111–4.

    CAS  PubMed  Google Scholar 

  37. Hulkova H, Elleder M. Distinctive histopathological features that support a diagnosis of cholesterol ester storage disease in liver biopsy specimens. Histopath. 2012;60:1107–13.

    Article  Google Scholar 

  38. Himes RW, Barlow SE, Bove K, Quintanilla NM, Sheridan R, Kohli R. Lysosomal acid lipase deficiency unmasked in two children with nonalcoholic fatty liver disease. Pediatrics. 2016;138:e20160214.

    Article  PubMed  Google Scholar 

  39. Guardamagna O, Abello O, Anfossi G, Pirro M. Lipoprotein (a) and family history of cardiovascular disease in children with familial dyslipidemias. J Pediatr. 2011;159:314–9.

    Article  CAS  PubMed  Google Scholar 

  40. von Dahl S, Harzer K, Rolfs A, Albrecht B, Niederau C, Vogt C, van Weely S, Aerts J, Muller G, Haussinger D. Heptospenomegaliclipidosis: what unless Gaucher? Adult cholesteryl ester storage disease (CESD) with anemia, mesenteric lipodystrophy, increased plasma chitotriosidase activity and a homozygous lysosomal acid lipase -1 exon 8 splice junction mutation. J Hepatol. 1999;31:741–6.

    Article  Google Scholar 

  41. Gasche C, Aslanidis C, Kain R, Exner M, Helbich T, Dejaco C, Schmitz G, Ferenci P. A novel variant of lysosomal acid lipase in cholesteryl ester storage disease associated with mild phenotype and improvement on lovastatin. J Hepatol. 1997;27:744–50.

    Article  CAS  PubMed  Google Scholar 

  42. Elleder M, Ledvinova J, Cieslar P, Kuhn R. Subclinical course of cholesterol ester storage disease (CESD) diagnosed in adulthood. Virchows Archiv A Pathol Anat. 1990;416:357–65.

    Article  CAS  Google Scholar 

  43. Cagle PT, Ferry GD, Beaudet AL, Hawkins EP. Pulmonary hypertension in an 18-year old girl with cholesteryl ester storage disease (CESD). Am J Med Genet. 1986;24:711–22.

    Article  CAS  PubMed  Google Scholar 

  44. Sloan HR, Frederickson DS. Enzyme deficiency in cholesteryl ester storage disease. J Clin Invest. 1972;51:1923–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Beaudet AL, Ferry GD, Nichols BL, Rosenberg HS. Cholesteryl ester storage disease: clinical, biochemical and pathological studies. J Pediatr. 1977;90:910–4.

    Article  CAS  PubMed  Google Scholar 

  46. Haller W, Sharif K, Millar AJW, Brown RM, McKiernan PJ. Gallbladder dysfunction in cholesterol ester storage disease. J Pediatr Gastroenterol Nutr. 2010;50:555–8.

    PubMed  Google Scholar 

  47. Zhang B, Porto AF. Cholesteryl ester storage disease: protean presentations of lysosomal acid lipase deficiency. J Pediatr Gastroenterol Nutr. 2013;56:682–5.

    Article  CAS  PubMed  Google Scholar 

  48. Horton JD, Cohen JC, Hobbs HH. PCSK9: a convertase that coordinates LDL catabolism. J Lipid Res. 2009;50:S172–7.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Chatrath H, Keilin S, Attar BM. Cholesterol ester storage disease (CESD) diagnosed in an asymptomatic adult. Dig Dis Sci. 2009;54:168–73.

    Article  PubMed  Google Scholar 

  50. Soutar AK, Naoumova RP. Mechanisms of disease: genetic causes of familial hypercholesterolemia. Nat Clin Pract Cardiovasc Med. 2007;4:214–25.

    Article  CAS  PubMed  Google Scholar 

  51. Bays HE, Jones PH, Orringer CE, Brown WV, Jacobson TA. National lipid association annual summary of clinical lipidology. J Clin Lipidol. 2016;10:S1–43.

    Article  PubMed  Google Scholar 

  52. Nordestgaard BG, Chapman MJ, Humphries SE, Ginsberg HN, Masana L, Descamps OS, Wiklund O, Hegele RA, Raal FJ, Defesche JC, Wiegman A, Santos RD, Watts GF, Parhofer KG, Hovingh GK, Kovanen PT, Boileau C, Averna M, Boren J, Bruckert E, Catapano AL, Kuivenhoven JA, Pajukanta P, Ray K, Stalenhoef AF, Stroes E, Taskinen MR, Tybjaerg-Hansen A, European Atherosclerosis Society Consensus Panel. Familial hypercholesterolemia is underdiagnosed and untreated in the general population: guidance for clinicians to prevent coronary heart disease: Consensus Statement of the European Atherosclerosis Society. Eur Heart J. 2013;34:3478–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Veerkamp MJ, de Graaf J, Bredie SJH, Hendricks JCM, Demacker PNM, Stalenhoef AFH. Diagnosis of familial combined hyperlipidemia based on lipid phenotype express in 32 families. Results of a 5-year follow-up study. Arterioscler Thromb Vasc Biol. 2002;22:274–82.

    Article  CAS  PubMed  Google Scholar 

  54. Pratt DS, Kaplan MM. Evaluation of abnormal liver-enzyme results in asymptomatic patients. NEJM. 2000;342:1266–71.

    Article  CAS  PubMed  Google Scholar 

  55. Hamilton J, Jones J, Srivastava R, Galloway P. A new method for the measurement of lysosomal acid lipase in dried blood spots using the inhibitor Lalistat 2. Clin Chem Acta. 2012;413:1207–10.

    Article  CAS  Google Scholar 

  56. Mukherjee M. Human digestive and metabolic lipases-a brief review. J Mol Catal B Enzym. 2003;22:369–76.

    Article  CAS  Google Scholar 

  57. Rosenbaum AJ, Cosner CC, Mariani CJ, Maxfield FR, Wiest O, Helquist P. Thiadiazole carbamates: potent inhibitors of lysosomal acid lipase and potential Niemann–Pick type C therapeutics. J Med Chem. 2010;53:5281–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Burton BK, Balwani F, Feillet F, Baric TA, Burrow C, Camarena Grande C, Coker M, Consuelo-Sanchez A, Deegan P, DiRicco M, Enns GM, Erbe R, Ezgu F, Ficicioglu C, Furuya KN, Kane J, Laukaitis C, Mengel E, Neilan EG, Nightengale S, Peters H, Scarpa M, Schwab KO, Smolka V, Valayannopoulos V, Wood M, Goodman Z, Yang Y, Eckert S, Rojas-Caro S, Quinn AG. A phase 3 trial of sebelipase alfa in lysosomal acid lipase deficiency. New Engl J Med. 2015;373:1010–20.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  60. Cholesterol Treatment Trialists’ (CTT) Collaboration, Fulcher J, O’Connell R, Voysey M, Emberson J, Blackwell L, Mihaylova B, Simes J, Collins R, Kirby A, Colhoun H, Braunwald E, LaRosa J, Pedersen TR, Tonkin A, Davis B, Sleight P, Franzosi MG, Baigent C, Keech A. Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomized trials. Lancet. 2015;385:1397–405.

    Article  Google Scholar 

  61. Reiner Z. Statins in the primary prevention of cardiovascular disease. Nat Rev Cardiol. 2013;10:453–64.

    Article  CAS  PubMed  Google Scholar 

  62. Tadiboyina VT, Liu DM, Miskie BA, Wang J, Hegele RA. Treatment of dyslipidemia with lovastatin and ezetimibe in an adolescent with cholesterol ester storage disease. Lipids Health Dis. 2005;4:1–6.

    Article  Google Scholar 

  63. Levy R, Ostlund RE, Schonfeld G, Wong P, Semenkovich CF. Cholesteryl ester storage disease: complex molecular effects of chronic lovastatin therapy. J Lipid Res. 1992;33:1005–15.

    CAS  PubMed  Google Scholar 

  64. Rader DJ. Lysosomal acid lipase deficiency-a new therapy for a genetic lipid disease. New Engl J Med. 2015;373:1071–3.

    Article  PubMed  Google Scholar 

  65. Tarantino MD, McNamara DJ, Granstrom P, Ellefson RD, Unger EC, Udall JN. Lovastatin therapy for cholesterol ester storage disease in two sisters. J Pediatr. 1991;118:131–5.

    Article  CAS  PubMed  Google Scholar 

  66. Rassoul F, Richter V, Lohse P, Naumann A, Purschwitz K, Keller E. Long-term administration of the HMG CoA reductase inhibitor lovastatin in two patients with cholesteryl ester storage disease. J Clin Pharmacol Therap. 2001;39:199–204.

    CAS  Google Scholar 

  67. Leone L, Ippoliti PF. Use of simvastatin plus cholestyramine in the treatment of lysosomal acid lipase deficiency. J Pediatr. 1991;119:1008–9.

    Article  CAS  PubMed  Google Scholar 

  68. Leone L, Ippoliti PF, Antonicelli R, Balli F, Gridelli B. Treatment and liver transplantation for cholesterol ester storage disease. J Pediatr. 1995;127:509.

    Article  CAS  PubMed  Google Scholar 

  69. Bisceglie AM, Ishak KG, Rabin L, Hoeg JM. Cholesteryl ester storage disease: hepatopathology and effects of therapy with lovastatin. Hepatol. 1990;11:764–72.

    Article  Google Scholar 

  70. Krivit W, Peters C, Dusenbery K, Ben-Yoseph Y, Ramsey NK, Wagner JE, Andersen R. Wolman disease successfully treated by bone marrow transplantation. Bone Marrow Transplant. 2000;26:567–70.

    Article  CAS  PubMed  Google Scholar 

  71. Stein J, Gary BZ, Dror Y, Fenig E, Zeigler M, Yaniv I. Successful treatment of Wolman disease by unrelated umbilical cord blood transplantation. Eur J Pediatr. 2007;166:663–6.

    Article  PubMed  Google Scholar 

  72. Kyriakides EC, Paul B, Baliant JA. Lipid accumulation and acid lipase deficiency in fibroblasts from a family with Wolman’s disease, and their apparent correction in vitro. J Lab Clin Med. 1972;80:810–6.

    CAS  PubMed  Google Scholar 

  73. Brown MS, Sobhani MK, Brunschede GY, Goldstein JL. Restoration of a regulatory response to low density lipoprotein in acid lipase-deficient human fibroblasts. J Biol Chem. 1976;251:3277–86.

    CAS  PubMed  Google Scholar 

  74. Krivit W, Freese D, Chan KW, Kulkarni R. Wolman’s disease: a review of treatment with bone marrow transplantation and considerations for the future. Bone Marrow Transplant. 1992;10(Suppl 1):97–101.

    PubMed  Google Scholar 

  75. Tolar J, Petryk A, Khan K, Bjoraker KJ, Jessurum J, Dolan M, Kivisto T, Charnas L, Shapiro EG, Orchard PJ. Long-term metabolic, endocrine, and neuropsychological outcome of hematopoietic cell transplantation for Wolman disease. Bone Marrow Transplant. 2009;43:21–7.

    Article  CAS  PubMed  Google Scholar 

  76. Arterburn JN, Lee WM, Wood RP, Shaw BW, Markin RS. Orthoptic liver transplantation for cholesterl ester storage disease. J Clin Gastroenterol. 1991;13:482–5.

    Article  CAS  PubMed  Google Scholar 

  77. Ferry GD, Whisennand HH, Finegold MJ, Alpert E, Glombicki A. Liver transplantation for cholesteryl ester storage disease. J Pediatr Gastroenterol Nutr. 1991;12:376–8.

    Article  CAS  PubMed  Google Scholar 

  78. Kale AS, Ferry GD, Hawkins EP. End-stage renal disease in a patient with cholesteryl ester storage disease following successful liver transplantation and cyclosporine immunosuppression. J Pediatr Gastroenterol Nutr. 1995;20:95–7.

    Article  CAS  PubMed  Google Scholar 

  79. Du H, Duanmu M, Witte D, Grabowski GA. Targeted disruption of the mouse lysosomal acid lipase gene: long-term survival with massive cholesteryl ester and triglyceride storage. Human Mol Genet. 1998;7:1347–54.

    Article  CAS  Google Scholar 

  80. Von Figura K, Hasilik A. Lysosomal enzymes and their receptors. Annu Rev Biochem. 1986;55:167–93.

    Article  Google Scholar 

  81. Du H, Schiavi S, Levine M, Mishra J, Heur M, Grabowski GA. Enzyme therapy for lysosomal acid lipase deficiency in the mouse. Human Mol Genet. 2001;10:1639–48.

    Article  CAS  Google Scholar 

  82. Du H, Schiavi S, Wan N, Levine M, Witte DP, Grabowski GA. Reduction of atherosclerotic plaques by lysosomal acid lipase supplementation. Arterioscler Thromb Vasc Biol. 2004;24:147–54.

    Article  CAS  PubMed  Google Scholar 

  83. Du H, Levine M, Ganesa C, Witte DP, Cole ES, Grabowski GA. The role of mannosylated enzyme and the mannose receptor in enzyme replacement therapy. Am J Hum Genet. 2005;77:1061–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Du H, Cameron TL, Garger SJ, Pogue GP, Hamm LA, White E, Hanley KM, Grabowski GA. Wolman disease/cholesteryl ester storage disease: efficacy of plant-produced human lysosomal acid lipase in mice. J Lipid Res. 2008;49:1646–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Anderson RA, Sando GN. Cloning and expression of cDNA encoding human lysosomal acid lipase/cholesteryl ester hydrolase. J Biol Chem. 1991;266:22479–84.

    CAS  PubMed  Google Scholar 

  86. Quinn AG, Harvey A, Chen M, Christmann L, Leavitt M, Hu W. SBC-102, a recombinant enzyme replacement therapy corrects key abnormalities due to lysosomal acid lipase deficiency. Washington, DC: American Society of Human Genetics (ASHG); 2010.

    Google Scholar 

  87. Balwani M, Breen C, Enns GM, Deegan PB, Honzik T, Jones S, Kane JP, Malinova V, Sharma R, Stock EO, Valayannopoulos V, Wraith JE, Burg J, Eckert S, Schnieder E, Quinn AG. Clinical Effect and safety profile of recombinant human lysosomal acid lipase in patients with cholesteryl ester storage disease. Hepatol. 2013;58:950–7.

    Article  CAS  Google Scholar 

  88. Friedman M, Valayannopoulos V, Camarena CG, Sanchez AC, Kane J, Kostyleva M, Tylki-Szymanska A, Sokal E, Sharma R, Rojas-Caro S, Wolfendale N, Burton BK. Safety findings from 3 trials of treatment with sebelipase alfa in children and adults with lysosomal acid lipase deficiency. Mol Genet Metabol. 2016;117:S47.

    Article  Google Scholar 

  89. Jones SA, Brassier A, Hughes J, Plantaz D, Vara R, Breen C, Gargus JJ, Valayannopoulos V. Effect of sebelipase alfa on survival and liver function in infants with rapidly progressive lysosomal acid lipase deficiency: 2 year follow-up data. Mol Genet Metabol. 2016;117:S63.

    Article  Google Scholar 

  90. Goff DC, Lloyd-Jones DM, Bennett G, Coady S, D’Agostino RB, Gibbons R, Greenland P, Lackland DT, Levy D, O’Donnell CJ, Robinson JG, Schwartz JS, Shero ST, Smith SC, Sorlie P, Stone NJ, Wilson PWF. 2013 ACC/AHA guideline on the assessment of cardiovascular risk. A report of the American College of Cardiology/American Heart Association task force on practice guidelines. Circulation. 2014;129:S49–73.

    Article  PubMed  Google Scholar 

  91. Huntzinger A. AHA guidelines on cardiac CT for assessing coronary artery disease. Am Fam Physician. 2008;77:704–6.

    Google Scholar 

  92. Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics. 2011;128:S1–44.

    Article  Google Scholar 

  93. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the national cholesterol education program (NCEP). JAMA. 2001;285:2486–97.

    Article  Google Scholar 

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Correspondence to James J. Maciejko.

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James J. Maciejko has received speaker honoraria from Alexion, Amgen, Sanofi, and Merck.

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An erratum to this article is available at http://dx.doi.org/10.1007/s40256-017-0228-1.

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Maciejko, J.J. Managing Cardiovascular Risk in Lysosomal Acid Lipase Deficiency. Am J Cardiovasc Drugs 17, 217–231 (2017). https://doi.org/10.1007/s40256-017-0216-5

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