Lysosomal storage disorders as the cause of dyslipoproteinemia

Authors: Anna Hlavatá;  Katarína Juríčková
Authors‘ workplace: Detská klinika LF UK a NÚDCH, Centrum dedičných metabolických porúch, Bratislava
Published in: AtheroRev 2018; 3(3): 184-191
Category: Reviews


Lysosomal storage disorders (LSDs) belong to group of rare, inborn, inherited diseases. They are caused by insufficient activity of certain lysosomal enzymes, by error of a transport protein or by malfunction of an enzymatic activator. Onset of symptoms occur anytime from infancy until adulthood. Early onset forms of disorders are commonly linked with severe natural course, quick progression of organ failure and with generally poor prognosis. Late onset of disorder, during adulthood, is commonly linked with mild form of disease. Without appropriate therapy they also lead to sever organ failure. Natural course of these disorders is multisystemic with progression of clinical impairments. The most affected are metabolic active tissues and organs: bone marrow, liver, bones, muscles, myocardium or central nervous system. Although dyslipoproteinemia is a common finding during routine biochemical screening it is often overseen and can prolong the time needed for establishing the right diagnosis. Authors of this paper are discussing some of the LSD connected with dyslipoproteinemia, which are currently treatable. They are describing clinical presentation, diagnostic procedures and actual therapeutic approaches of inborn errors of metabolism.

Key words:

diagnostic approach, dyslipoproteinemia, enzyme replacement therapy, lysosomal storage disorders, substrate reducing therapy

Received: 24. 9. 2018

Accepted: 1. 10. 2018

  1. de Duve C, Wattiaux R. Functions of lysosomes. Annu Rev Physiol 1966; 28: 435–492. Dostupné z DOI: <>.
  2. Kuehnel, W. Color Atlas of Cytology, Histology and Microscopic Anatomy. 4th ed. Thieme 2003: 34. ISBN: 3135624048.
  3. Settembre C, Fraldi A, Jahreiss L et al. A block of autophagy in lysosomal storage disorders. Hum Mol Genet 2008; 17(1): 119–129. Dostupné z DOI: <>.
  4. Schulze H, Sandhoff K. Lysosomal Lipid Storage Diseases. Cold Spring Harb Perspect Biol 2011; 3(6). pii: a004804. Dostupné z DOI: <>.
  5. Ferreira CR, Gahl WA. Lysosomal storage diseases. Transl Sci Rare Dis 2017; 2(1–2): 1–71. Dostupné z DOI: <>.
  6. Zhao G-J, Yin K, Fu Y-C et al. The interaction of ApoA-I and ABCA1 triggers signal transduction pathways to mediate efflux of cellular lipids. Mol Med Camb Mass 2012; 18: 149–158. Dostupné z DOI: <>.
  7. Neufeld EB, Stonik JA, Demosky SJ et al. The ABCA1 transporter modulates late endocytic trafficking: insights from the correction of the genetic defect in Tangier disease. J Biol Chem 2004; 279(15): 15571–15578. Dostupné z DOI: <>.
  8. Glaros EN, Kim WS, Quinn CM et al. Glycosphingolipid accumulation inhibits cholesterol efflux via the ABCA1/apolipoprotein A-I pathway: 1-phenyl-2-decanoylamino-3-morpholino-1-propanol is a novel cholesterol efflux accelerator. J Biol Chem 2005; 280(26): 24515–2423. Dostupné z DOI: <>.
  9. Schueler U, Kaneski C, Remaley A et al. A Short Synthetic Peptide Mimetic of Apolipoprotein A1 Mediates Cholesterol and Globotriaosylceramide Efflux from Fabry Fibroblasts. JIMD Rep 2016; 29: 69–75. Dostupné z DOI: <>.
  10. Zimmermann A, Grigorescu-Sido P, Rossmann H et al. Dynamic changes of lipid profile in Romanian patients with Gaucher disease type 1 under enzyme replacement therapy: a prospective study. J Inherit Metab Dis 2013; 36(3): 555–563. Dostupné z DOI: <–012–9529–3>.
  11. Stepien KM, Hendriksz CJ. Lipid profile in adult patients with Fabry disease – Ten-year follow up. Mol Genet Metab Rep 2017; 13: 3–6. Dostupné z DOI: <>.
  12. Ikonen E. Cellular cholesterol trafficking and compartmentalization. Nat Rev Mol Cell Biol 2008; 9(2): 125–138. Dostupné z DOI: <>.
  13. Sloan HR, Fredrickson DS. Enzyme deficiency in cholesteryl ester storage disease. J Clin Invest 1972; 51(7): 1923–1926. Dostupné z DOI: <>.
  14. Fouchier SW, Defesche JC. Lysosomal acid lipase A and the hypercholesterolaemic phenotype. Curr Opin Lipidol 2013; 24/4): 332–328. Dostupné z DOI: <>.
  15. Tadiboyina VT, Liu DM, Miskie BA et al. Treatment of dyslipidemia with lovastatin and ezetimibe in an adolescent with cholesterol ester storage disease. Lipids Health Dis 2005; 4: 26. Dostupné z DOI: <–511X-4–26>.
  16. Elleder M, Poupětová H, Ledvinová J et al. Deficit kyselé (lysozomální) lipázy. Přehled českých pacientů. Čas Lék Čes 1999; 138(23): 719–724.
  17. Mattošová S, Chandoga J, Hlavatá A et al. Spectrum of GBA mutations in patients with Gaucher disease from Slovakia: identification of five novel mutations. Isr Med Assoc J 2015; 17(3): 166–170.
  18. Mattosova S, Hlavata A, Spalek P et al. Late onset form of Pompe disease. Bratisl Lek Listy 2015; 116(8): 502–505.
  19. Jameson E, Jones S, Wraith JE. Enzyme replacement therapy with laronidase (Aldurazyme(®)) for treating mucopolysaccharidosis type I. Cochrane Database Syst Rev 2013; (11): CD009354. Dostupné z DOI: <>.
  20. Andersson H, Kaplan P, Kacena K et al. Eight-year clinical outcomes of long-term enzyme replacement therapy for 884 children with Gaucher disease type 1. Pediatrics 2008; 122(6): 1182–1190. Dostupné z DOI: <–2144>.
  21. Starzyk K, Richards S, Yee J et al. The long-term international safety experience of imiglucerase therapy for Gaucher disease. Mol Genet Metab 2007; 90(2): 157–163. Dostupné z DOI: <>.
  22. Fecarotta S, Romano A, Della Casa R et al. Long term follow-up to evaluate the efficacy of miglustat treatment in Italian patients with Niemann-Pick disease type C. Orphanet J Rare Dis 2015; 10: 22. Dostupné z DOI: <–015–0240-y>.
  23. Capablo JL, Franco R, de Cabezón AS et al. Neurologic improvement in a type 3 Gaucher disease patient treated with imiglucerase/miglustat combination. Epilepsia 2007; 48(7): 1406–1408. Dostupné z DOI: <–1167.2007.01074.x>.
  24. Goláň L. Migalastat v terapii Fabryho choroby. Interní Medicína Praxi 2017; 19(3): 167–170.
  25. Mistry PK, Cappellini MD, Lukina E et al. A reappraisal of Gaucher disease-diagnosis and disease management algorithms. Am J Hematol 2011; 86(1): 110–115. Dostupné z DOI: <>.
  26. Kaplan P, Baris H, De Meirleir L et al. Revised recommendations for the management of Gaucher disease in children. Eur J Pediatr 2013; 172(4): 447–458. Dostupné z DOI: <–012–1771-z>.
  27. Elias AF, Johnson MR, Boitnott JK et al. Neonatal cholestasis as initial manifestation of type 2 Gaucher disease: a continuum in the spectrum of early onset Gaucher disease. JIMD Rep 2012; 5: 95–98. Dostupné z DOI: <>.
  28. Park JK, Orvisky E, Tayebi N et al. Myoclonic epilepsy in Gaucher disease: genotype-phenotype insights from a rare patient subgroup. Pediatr Rep 2003; 53(3): 387–395. Dostupné z DOI: <>.
  29. Belmatoug N, Di Rocco M, Fraga C et al. Management and monitoring recommendations for the use of eliglustat in adults with type 1 Gaucher disease in Europe. Eur J Intern Med 2017; 37:25–32. Dostupné z DOI: <>.
  30. Waldek S, Feriozzi S. Fabry nephropathy: a review – how can we optimize the management of Fabry nephropathy? BMC Nephrol 2014; 15: 72. Dostupné z DOI: <–2369–15–72>.
  31. Bacharova L, Ugander M. Left ventricular hypertrophy: The relationship between the electrocardiogram and cardiovascular magnetic resonance imaging. Ann Noninvasive Electrocardiol 2014; 19(6): 524–533. Dostupné z DOI: <>.
  32. Schiffmann R, Ries M. Fabry Disease: A Disorder of Childhood Onset. Pediatr Neurol 2016; 64: 10–20. Dostupné z DOI: <>.
  33. Vanier MT. Niemann-Pick diseases. Handb Clin Neurol 2013; 113: 1717–1721. Dostupné z DOI: <–0-444–59565–2.00041–1>.
  34. Mengel E, Klünemann HH, Lourenço CM et al. Niemann-Pick disease type C symptomatology: an expert-based clinical description. Orphanet J Rare Dis 2013; 8: 166. Dostupné z DOI: <–1172–8-166>.
  35. Jahnova H, Dvorakova L, Vlaskova H et al. Observational, retrospective study of a large cohort of patients with Niemann-Pick disease type C in the Czech Republic: a surprisingly stable diagnostic rate spanning almost 40 years. Orphanet J Rare Dis 2014; 9: 140. Dostupné z DOI: <–014–0140–6>.
  36. Hoeg JM, Demosky SJ, Pescovitz OH et al. Cholesteryl ester storage disease and Wolman disease: phenotypic variants of lysosomal acid cholesteryl ester hydrolase deficiency. Am J Hum Genet 1984; 36(6): 1190–1203.
  37. Maciejko JJ. Managing Cardiovascular Risk in Lysosomal Acid Lipase Deficiency. Am J Cardiovasc Drugs 2017; 17(3): 217–231. Dostupné z DOI: <–017–0216–5>. Erratum in Erratum to: Managing Cardiovascular Risk in Lysosomal Acid Lipase Deficiency. [Am J Cardiovasc Drugs. 2017].
  38. Erwin AL. The role of sebelipase alfa in the treatment of lysosomal acid lipase deficiency. Therap Adv Gastroenterol 2017; 10(7): 553–562. Dostupné z DOI: <>.
Angiology Diabetology Internal medicine Cardiology General practitioner for adults
Forgotten password

Don‘t have an account?  Create new account

Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.


Don‘t have an account?  Create new account