Wilson's Disease: Monocentric Experiences Over a Period of 16 Years

Abstract

Background: Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism. The objective of this study is to present diagnostic pitfalls and long time follow-up data in Wilson disease.

Patients/Methods: We studied 21 WD patients and 14 heterozygote carriers aged 2–43 years, retrospectively. 18 WD patients presented liver disease, three had mixed neurological and hepatic involvement and 9 patients underwent orthotopic liver transplantation (OLT).

Results: The median age at diagnosis of WD children without OLT was 10.16±3.8 (range, 5–16). All of females and younger age categories of patients prevailed in acute liver failure group. Serum ceruloplasmine levels were below 0.2 g/l in about ⅓ of WD carriers (X¯=0.27±0.09 g/l) and nearly ⅔ of children with WD (X¯= 0.21±0.13 g/l). A statistically significant difference (p<0.05) in the 24-h excretion of copper in urine was noticed between healthy controls, children with WD and WD heterozygote carriers. As diagnostic important proved the copper content of more than 250 μg/g hepatic dry weight. The Kayser-FleischerŽs ring was not observed in children. Ceruloplasmine, haemoglobin, ALT, ALP and plasma albumin were significantly different between fulminant and non-fulminant WD and could be used as indirect markers in evaluation of urgent OLT.

Conclusion: Detection of WD in children remains very difficult. The most important investigation is liver biopsy with the assessment of liver copper. Genetic analysis may help in doubtful cases.

Zusammenfassung

Hintergrund: Morbus Wilson (MW) ist eine autosomal-rezessive Störung des Kupferstoffwechsels. Das Ziel dieser Studie ist es, klinische Probleme bei der Diagnostik und die Daten der Langzeitbeobachtung von Morbus Wilson zu präsentieren.

Patienten und Methoden: Wir haben 21 MW-Patienten und 14 heterozygote Träger im Alter von 2 bis 43 Jahren retrospektiv analysiert. Von den MW-Patienten haben 18 an einer isolierten Lebererkrankung und 3 an einer gemischt-neurologisch-hepatischen Störung gelitten; insgesamt 9 Patienten haben sich einer orthotopen Lebertransplantation (OLT) unterzogen.

Ergebnisse: Das Durchschnittsalter bei Diagnose der MW-Patienten ohne OLT war 10,16±3,8 Jahre (Bereich 5–16). Alle jungen Frauen und Mädchen gehören in die Gruppe von Patienten mit akuten Leberstörungen. Bei ca ⅓ von MW-Trägern (X¯ 0,27±0,09 g/l) und fast ⅔ von Kindern mit MW (X¯ 0,21±0,13 g/l) waren die Werte des Ceruloplasmins im Serum <0,2 g/l. Bei gesunden Kontrollpersonen, Kindern mit MW und heterozygoten MW-Trägern wurde eine statistisch signifikante Differenz (p<0,05) in der 24-Stunden-Kupferausscheidung im Urin beobachtet. Als wichtiges Untersuchungsmerkmal hat sich ein Kupfergehalt von > 250 μg/g im Lebertrockengewicht erwiesen. Der Kayser-Fleischer-Ring wurde bei Kindern nicht beobachtet. Ceruloplasmin, Hämoglobin, ALT, ALP und Plasmaalbumin haben bei fulminantem und nicht-fulminantem MW signifikante Unterschiede aufgewiesen und könnten als indirekte Marker für die Entscheidung für eine dringliche OLT verwendet werden.

Schlussfolgerung: Die Diagnose des MW bei Kindern bleibt kompliziert. Die wichtigste Untersuchungsmethode ist die Leberbiopsie mit Bestimmung des Kupfergehaltes in der Leber. Die genetische Analyse kann in unklaren Fällen behilflich sein.

Wilson disease - copper metabolism - orthotopic liver transplantation - children

Morbus Wilson - Kupferstoffwechsel - orthotope Lebertransplantation - Kinder

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