Treatment of copper associated liver disease in childhood.
OBJECTIVE
Copper associated liver disease is accompanied with high liver copper concentrations and progressive liver disease in infancy or childhood. The disease is thought to be due to excessive dietary copper overload (copper-enriched water supply) and in addition to be based on a genetic predisposition. Treatment with penicillamine in Indian childhood disease, which probable has the same etiology, is effective when it is started early enough as well as in Wilson's disease. We aimed to describe the clinical features of copper associated liver disease and report our experience with different treatment options in German children.


RESULTS
Two boys presented at the age of 6 and 10 months with abdominal distension due to hepatosplenomegaly. The diagnosis of copper associated liver disease was made based on feeding history, standard liver function parameters, liver biopsy and assessment of dry weight copper concentration and urinary excretion of copper. Both had micronodular cirrhosis, ballooning of hepatocytes and Mallory bodies. In child A improvement of liver function was observed after introduction of penicillamine therapy and copper-reduced diet. The treatment was stopped after 18 months, when normalisation of copper concentration in the liver had occured. In child B acute liver failure developed despite initiation of treatment. The boy was transplanted successfully. Both children are presently healthy 10 years after transplantation and 4 years after begin of chelating therapy, respectively.


CONCLUSIONS
We conclude, that early chelating therapy with penicillamine can be successful in children with copper associated liver disease. In case of delayed diagnosis and acute liver failure liver transplantation is necessary. Our case reports highlight the urgent need of rapid diagnosis of copper associated liver disease in order to initiate early chelating therapy. Copper associated liver disease should obviously be considered in liver disease of unknown origin. Possible causes of excessive dietary copper intake should be ascertained.
Rodeck
B
B
Zentrum für Kinderheilkunde und Humangenetik, Medizinische Hochschule Hannover, D-30623 Hannover, Germany. rodeck.burkhard@mh-hannover.de
Kardoff
R
R
Melter
M
M
D002614:Chelating Agents / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury; D003300:Copper / Q000633:toxicity*; D004326:Drinking; D005858:Germany; D006801:Humans; D007223:Infant; D008107:Liver Diseases / Q000188:drug therapy* / Q000601:surgery; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000188:drug therapy / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D010396:Penicillamine / Q000627:therapeutic use; D014874:Water Pollutants, Chemical / Q000633:toxicity; D014881:Water Supply
D002614:Chelating Agents; D014874:Water Pollutants, Chemical; D003300:Copper; D010396:Penicillamine