RSS-Feed abonnieren
DOI: 10.1055/s-0033-1334900
Kontrolle der Zinktherapie bei Morbus Wilson mit dem oralen Radiokupfertest
Monitoring Therapy in Wilson’s Disease by the Oral Radiocopper TestPublikationsverlauf
Publikationsdatum:
22. Februar 2013 (online)
![](https://www.thieme-connect.de/media/aktneu/201304/lookinside/thumbnails/10.1055-s-0033-1334900-1.jpg)
Zusammenfassung
Hintergrund:
Der Morbus Wilson ist eine seltene Kupferstoffwechselstörung, die bei früher Diagnosestellung und konsequenter Therapie eine sehr gute Prognose hat. Nebenwirkungen oder eine nachlassende Wirksamkeit können Komplikationen einer medikamentösen Langzeitbehandlung sein. Besonders bei der Behandlung mit Zink haben sich Berichte über ein Versagen der Therapie gehäuft.
Material und Methoden:
Bei 58 Patienten mit einem Morbus Wilson unter Langzeittherapie wurde in insgesamt 91 Mal ein oraler Radiokupfertest durchgeführt und damit das Ausmaß der enteralen Resorptionshemmung von Kupfer bestimmt. 84 Messungen erfolgten unter einer Zinkmedikation, eine unter D-Penizillamin und sechs unter einer Behandlung mit Trien.
Ergebnisse:
Die mit Zink behandelten Patienten zeigten in 48 Tests eine ausreichende, in 36 Fällen aber eine ungenügende Hemmung der enteralen Kupferresorption. Für Trien konnte eine partielle enterale Resorptionshemmung von Kupfer gezeigt werden.
Schlussfolgerung:
Die Behandlung des Morbus Wilson erfordert in jedem Fall eine regelmäßige Kontrolle. Der orale Radiokupfertest erlaubt eine quantitative Aussage zum Einfluss von Zink auf die Kupferresorption beim Morbus Wilson. Sein Nutzen muss durch weitere Studien näher definiert werden.
Abstract
Background:
Wilson’s disease is a rare autosomal recessive disorder of hepatic copper transport leading to an inhibition of the biliary excretion of copper. Overloads of the metal mainly in the liver and basal ganglia lead to hepatic but also to extrapyramidal motor as well as psychiatric clinical symptoms. Depending on the stage of the disease, therapy with chelating drugs and zinc is possible but must be given lifelong without longer interruptions. With early diagnosis and consequent treatment, the prognosis of Wilson’s disease is excellent and usually the need for liver transplantation can be avoided. Monitoring of treatment is essential because therapy with chelating penicillamine is complicated by side effects, triene is not always available and non-responders to zinc therapy are reported.
Method:
For the evaluation of the inhibition of enteral resorption of copper in our study an oral radiocopper test was performed in 58 patients with Wilson’s disease. Patients were given 10 MBq 64Cu and radioactivity was measured in serum at one and/or, respectively, 3 h after intake. Altogether 91 tests were evaluated.
Results:
No inhibition of copper resorption was found in 1 patient under penicillamine therapy. A partial inhibition of enteral resorption could be proved for triene in 6 patients. 48 tests showed a sufficient inhibition with zinc therapy. In 36 tests of the patients taking zinc the inhibition was proved to be not sufficient. In 6 of them it could be improved by increasing the dosage. Triene has been shown to inhibit the resorption of copper as well by this test. No inhibition is seen with penicillamine.
Conclusion:
The high prevalence of insufficient effectiveness of zinc therapy requires a continuous control. The radiocopper test allows an estimation of the influence of zinc on copper resorption in Wilsonʼs disease. Further studies have to be performed to evaluate the utility of this test.
-
Literatur
- 1 Cuthbert JA. Wilson’s disease: A new gene and animal model for an old disease. J Investig Med 1995; 43: 323-336
- 2 Westphal C. Über eine dem Bilde der cerebrospinalen grauen Degeneration ähnliche Erkrankung des centralen Nervensystems ohne anatomischen Befund, nebst einigen Bemerkungen über paradoxe Contraction. Arch Psychiatr 1983; 14: 87
- 3 Ferenci P. Pathophysiology and clinical features of Wilson disease. Metab Brain Dis 2004; 19: 229-239
- 4 Brewer GJ. Wilson’s disease: A clinician’s guide to recognition, diagnosis, and mangement. Boston Dordrecht London: Kluwer Academic Publishers; 2001
- 5 Hermann W, Kühn HJ, Merle U et al. Morbus Wilson. In: Leitlinien der Neurologie. 3. Auflage. Stuttgart: Thieme; 2005: 121-126
- 6 Walshe JM. Penicillamine. A new oral therapy for Wilson’s disease. Am J Med 1956; 21: 487-495
- 7 Walshe JM. Treatment of Wilson’s disease with trientine (triethylene tetramine) dihydrochloride. Lancet 1982; 1: 643-647
- 8 Shouwink G. De hepato-cerebrale degeneratie. Amsterdam: Thesis; 1961
- 9 Mills CF. Metabolic interactions of copper with other trace elements. In: Biological roles of copper, Ciba foundation symposium 79 Excerpta Medica. Amsterdam, Oxford, New York: 1980: 49-65
- 10 Hoogenraad TU, van den Hamer CJA. 3 years of continuous oral zinc therapy in 4 patients with Wilson’s disease. Acta Neurol Scand 1983; 67: 356-364
- 11 Schilsky M, Blank RR, Czaja MJ. Hepatocellular copper toxicity and its attenuation by zinc. J Clin Invest 1989; 84: 1562-1568
- 12 Lang CJ, Rabas-Kolominsky P, Engelhardt A et al. Fatal deterioration of Wilson's disease after institution of oral zinc therapy. Arch Neurol 1993; 50: 1007-1008
- 13 Walshe JM, Munro NA. Zinc-induced deterioration in Wilson’s disease aborted by treatment with penicillamine, dimercaprol, and a novel zero copper diet. Arch Neurol 1995; 52: 10-11
- 14 Weiss KH, Gotthardt DN, Klemm D et al. Zinc monotherapy is not as effective as chelating agents in treatment of Wilson disease. Gastroenterology 2011; 140: 1189-1198
- 15 Siegemund R, Günther K, Kühn HJ et al. Medikamentöse Beeinflussung der Bioverfügbarkeit von Kupfer. Zentbl Pharm Pharmakother Lab Diagn 1988; 127: 239-240
- 16 Biesold D, Günther K. Improved method for investigation of copper metabolism in patients with Wilson’s disease using 64Cu. Clinica Chimica Acta 1972; 42: 353-359
- 17 Sternlieb I, Morell AG, Tucker WP et al. The incorporation of copper into ceruloplasmin in vivo: studies with copper 64 and copper 67. J Clin Invest 1961; 40: 1834-1840
- 18 Walshe JM. Cause of death in Wilson disease. Mov Disord 2007; 15: 2216-2220
- 19 Van den Hamer CJA, Hoogenraad TU. 64Cu loading tests for monitoring zinc therapy in Wilson’s disease. Trace Elements in Medicine 1984; 1: 84-87
- 20 Wiggelinkhuizen M, Tilanus ME, Bollen EW et al. Systematic review: clinical efficacy of chelator agents and zinc in the initial treatment of Wilson disease. Aliment Pharmacol Ther 2009; 29: 947-958