Skip to main content
SpringerLink
Log in

Abnormal low density lipoproteins in children with familial hypercholesterolemia — Effet of polyanion exchange resins

Abnorme low density Lipoproteine bei Kindern mit familiärer Hypocholesterinämie — Ergebnis einer Behandlung mit Anionenaustauscherharzen auf Lipoproteinkonzentration und -zusammensetzung

  • Originalien
  • Published:
Klinische Wochenschrift Aims and scope Submit manuscript

Zusammenfassung

Bei 20 Kindern mit familiärer Hyperlipoproteinämie Typ IIa wurden die Serumlipide und -Lipoproteine vor und während einer lipidsenkenden Behandlung mit Anionenaustauscher-Kunstharzen untersucht. Die Zusammensetzung der low density Lipoproteine (LDL) wurde mit derjenigen der gesunden Geschwister der Patienten verglichen. Nach einer diätetischen Vorbehandlung von mindestens 12 Monaten Dauer erhielten die Patienten während je 8 Wochen Colestipol (0,5 g/kg Körpergewicht) und Colestyramin (0,6 g/kg Körpergewicht) in cross-over-Anordnung. Die Behandlung mußte bei 6 Kindern wegen Nebenwirkungen (Obstipation, Oberbauchbeschwerden) vorzeitig abgebrochen werden.

Neben zahlreichen Laborroutineparametern wurden Cholesterin, Triglyzeride und Phospholipide im Vollserum sowie Cholesterin, Triglyzeride und Apolipoprotein-B (Apo B) in isolierten Lipoproteinfraktionen nach Ultrazentrifugation gemessen. Apo B wurde mittels radialer Immunodiffusion bestimmt.

Die LDL der Patienten mit familiärer Hypercholesterinämie zeigten im Vergleich mit denen ihrer gesunden Geschwister eine Reduktion des Triglyzeridanteils um gegen 50%. Das Verhältnis Apo B: LDL-Cholesterin war dagegen bei Patienten und gesunden Kindern annähernd gleich. Diese abnorme LDL-Zusammensetzung wurde durch die Therapie mit Anionenaustauscher-Kunstharzen nicht verändert. Der HDL-Cholesterinspiegel war bei den Patienten mit familiärer Hypercholesterinämie signifikant niedriger als bei den gesunden Kindern — er blieb unter der lipidsenkenden Behandlung unverändert tief.

Das mit Colestyramin und Colestipol erzielte Behandlungsergebnis war sehr ähnlich, Gesamt- und LDL-Cholesterin wurden durch beide Substanzen um etwa 25% gesenkt. Die Triglyzerid- und Phospholipidspiegel wurden dagegen praktisch nicht beeinflußt.

Summary

In 20 children and adolescents with familial Type IIa hyperlipoproteinemia, serum lipids and lipoproteins were examined before and during treatment with polyanion exchange resins. The composition of LDL was compared to that of healthy siblings. The patients were given Colestyramine (0.6 g/kg body weight) and Colestipol (0.5 g/kg body weight) in a cross-over study for 8 weeks each, after they had been under dietary treatment for at least 12 months. In 6 children, drug treatment had to be stopped due to side-effects. The most common complaints were gastrointestinal discomfort and constipation.

Cholesterol, triglycerides and phopholipids were measured in whole serum and cholesterol, triglycerides and Apolipoprotein-B in isolated lipoprotein fractions after ultracentrifugation. Apo-B was determined by radial immunodiffusion.

The Apo-B: cholesterol ratio in whole serum and in the LDL fraction was identical in the patients and in the controls. The LDL triglyceride: Apo-B ratio, however, was about 50% lower in the patients. This abnormal LDL composition was not altered by therapy with polyanion exchange resins. HDL cholesterol levels were significantly lower in the patients than in healthy children, and remained low during therapy.

The decrease of total and LDL cholesterol (25%) and Apo-B (20%) was similar under both Colestipol and Colestyramine. Triglycerides and phospholipids showed no significant changes in therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Augustin, J., Middelhoff, G., Brown, W.V.: Metabolismus der Lipoproteine. In: Handbuch der Inneren Medizin, Vol. VII/4, Fettstoffwechsel, G. Schettler, H. Greten, G. Schlierf, D. Seidel (eds.), Berlin-Heidelberg-New York: Springer 1976, 219–264

    Google Scholar 

  2. Bagnall, T.F.: Composition of low density lipoproteins in children with familial hyperbetalipoproteinaemia and the effect of treatment. Clin. Chim. Acta42, 229–233 (1972

    Google Scholar 

  3. Bagnall, T.F., Lloyd, J.K.: Composition of low density lipoproteins in children with hyperlipoproteinaemia. Clin. Chim. Acta59, 271–276 (1975)

    Google Scholar 

  4. Bilheimer, D.W.: Low density lipoprotein metabolism and cholesterol synthesis in familial homozygous hypercholesterolemia: Influence of portocaval shunt surgery. In: Lipoprotein Metabolism, H. Greten (ed.), Berlin-Heidelberg-New York: Springer 1976, 44–55

    Google Scholar 

  5. Blum, C.B., Havlik, R.J., Morganroth, J.: Cholestyramine: An effective, twice-daily dosage regimen. Ann. Intern. Med.85, 287–289 (1976)

    Google Scholar 

  6. Farah, J.R., Kwiterovich, P.O., Jr., Neill, C.A.: Dose-effect relation of cholestyramin in children and young adults with familial hypercholesterolaemia. Lancet, Jan.8, 59–63 (1977)

    Google Scholar 

  7. Fellin, R., Briani, G., Balestrieri, P., Baggio, G., Baiocchi, M.R., Crepaldi, G.: Long-term effects of colestipol (U-26, 597 A) on plasma lipids in familial Type II hyperbetalipoproteinaemia. Atherosclerosis22, 431–445 (1975)

    Google Scholar 

  8. Fredrickson, D.S., Levy, R.I.: Familial hyperlipoproteinemia. In: “The metabolic basis of inherited disease.” Eds. J.B. Stanbury, J.B. Wyngaarden, D.S. Fredrickson, third edition. McGraw-Hill Book Company 1972, 545–614

  9. Glueck, C.J., Farr, S., Jr., Scheel, D., Steiner, P.: Colestipol and cholestyramin resin — Comparative effects in familial Type II hyperlipoproteinemia. JAMA222, 676–681 (1972)

    Google Scholar 

  10. Glueck, C.J., Fallat, R.W., Mellies, M., Tsang, R.C.: Pediatric familial type II hyperlipoproteinemia: Therapy with diet and colestipol resin. Pediatrics57, 68–74 (1976)

    Google Scholar 

  11. Glueck, C.J., Tsang, R.C., Fallat, R.W., Mellies, M.J.: Diet in children heterozygous for familial hypercholesterolemia. Amer. J. Dis. Child.131, 162–166 (1977)

    Google Scholar 

  12. Goldstein, J.L., Brown, M.S.: Binding and degradation of low density lipoproteins by cultured human fibroblasts. J. Biol. Chem.249, 5153–5162 (1974)

    Google Scholar 

  13. Greten, H., DeGrella, R., Klose, G., Rascher, W., de Gennes, J.L., Gjone, E.: Measurement of two plasma triglyceride lipases by an immunochemical method: Studies in patients with hypertriglyceridemia. J. Lipid Res.17, 203–210 (1976)

    Google Scholar 

  14. Gundersen, K., Cooper, E.E., Ruoff, G., Nikolai, T., Assenzo, J.R.: Cholesterol-lowering effect of colestipol hydrochloride given twice daily in hypercholesterolemic patients. Atherosclerosis25, 303–310 (1976)

    Google Scholar 

  15. Langer, I., Fredrickson, D.S., Levy, R.I.: Dietary and pharmacologic pertubation of beta lipoprotein (BLP) turnover. Circulation40 (Suppl. III), 14 (1969)

    Google Scholar 

  16. Lipid Research Clinic Program, Manual of Laboratory Operations, Vol. 1, Washington D.C.: U.S. Government Office (1974)

  17. Levy, R.I., Langer, I.: Hypolipidemic drugs and lipoprotein metabolism. Advanc. Exp. Med. Biol.26, 155–163 (1972)

    Google Scholar 

  18. Levy, R.I.: Drug therapy of hyperlipoproteinemia. JAMA235, 2334–2336 (1976)

    Google Scholar 

  19. Lowry, O.H., Roberts, N.R., Leiner, K.Y., Wu, N., Farr, L.: The quantitative histochemistry of brain. 1. Chemical method. J. Biol. Chem.207, 1 (1954)

    Google Scholar 

  20. Miller, C.J., Miller, N.E.: Plasma-high-density-lipoprotein concentration and development of ischaemic heart disease. Lancet1, 16–19 (1975)

    Google Scholar 

  21. Miller, N.E., Clifton-Bligh, P., Nestel, P.J., Whyte, H.M.: Controlled clinical trial of a new bile acid sequesterin resin, colestipol, in the treatment of hypercholesterolemia. Med. J. Australia1, 1223–1227 (1973)

    Google Scholar 

  22. Mills, G.L., Taylow, C.E., Chapman, M.J.: Low-density lipoproteins in patients homozygous for familial hyperbetalipoproteinaemia. Clin. Science and Mol. Medicine51, 221–231 (1976)

    Google Scholar 

  23. Miettinen, T.A.: Changes in cholesterol metabolism by colestipol hydrochloride in hypercholesterolemic patients. Eur. J. clin. Invest.4, 365–366 (1974)

    Google Scholar 

  24. Mordasini, R., Twelsick, F., Oster, P., Schellenberg, B., Raetzer, H., Heuck, C.C., Schlierf, G.: Eine vergleichende Untersuchung von Colestyramin und Colestipol bei Kindern und Heranwachsenden mit familiärer Hypercholesterinämie. Mschr. f. Kinderheilkde. (im Druck)

  25. Nestel, P.J., Miller, N.E., Clifton-Bligh, P.: Effects of colestipol and clofibrate on cholesterol turnover. Aus. NZ. J. Med.3, 630 (1973)

    Google Scholar 

  26. Parsons, W.B., Jr.: Comparison of cholesterol-reducing effects of cholestyramine and a new sequestrant of bile acids (colestipol). Circulation46, (Suppl. II) 272 (1972)

    Google Scholar 

  27. Reichl, D., Simens, L.A., Myant, N.B.: Clin. Sci. Mol. Med.47, 635–638 (1974)

    Google Scholar 

  28. Schlierf, G., Vogel, G., Heuck, C.C., Oster, P., Raetzer, H., Schellenberg, B.: Zur Diättherapie der familiären Hypercholesterinämie bei Kindern und Jugendlichen. Monatsschr. Kinderheilk. (im Druck)

  29. Segall, M.M., Fosbrooke, A.S., Lloyd, J.K., Wolff, O.H.: Treatment of familial hypercholesterolemia in children. Lancet, March28, 641–644 (1970)

    Google Scholar 

  30. Simons, L.A., Reichl, D., Myant, N.B., Mancini, M.: The metabolism of the apoprotein of plasma low density lipoprotein in familial hyperbetalipoproteinemia in the homozygous form. Atherosclerosis Res.21, 283–289 (1975)

    Google Scholar 

  31. Slack, J.: Risks of ischaemic heart disease in familial hyperlipoproteinemic states. LancetII, 1380 (1969)

    Google Scholar 

  32. Stein, E.A., Heimann, K.W.: Colestipol, clofibrate, cholestyramine and combination therapy in the treatment of familial hyperbetalipoproteinaemia. S. Afr. Med. J.49, 1252–1256 (1975)

    Google Scholar 

  33. Stone, N.J., Levy, R.I., Fredrickson, D.S., Verter, J.: Coronary artery disease in 116 kindred with familial type II hyperlipoproteinemia. Circulation XLIX:476 (1974)

    Google Scholar 

  34. Technicon clinical method No. 24, Technicon Instruments Tarrytown, N.Y. (1972)

Download references

Author information

Authors and Affiliations

  1. Klinisches Institut für Herzinfarktforschung an der Medizinischen Universitätsklinik Heidelberg, Germany

    R. Mordasini, F. Twelsiek, P. Oster, B. Schellenberg, H. Raetzer, C. C. Heuck & G. Schlierf

Authors
  1. R. Mordasini
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. Twelsiek
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. Oster
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. B. Schellenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H. Raetzer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. C. C. Heuck
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. G. Schlierf
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

These studies were supported by grants of the Schweizerische Nationalfonds and the Deutsche Forschungsgemeinschaft (Sonderforschungsbereich 90, Cardiovasculäres System)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mordasini, R., Twelsiek, F., Oster, P. et al. Abnormal low density lipoproteins in children with familial hypercholesterolemia — Effet of polyanion exchange resins. Klin Wochenschr 56, 805–808 (1978). https://doi.org/10.1007/BF01489714

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01489714

Schlüsselwörter

Key words

Search

Navigation