Wilson's disease is a treatable autosomal recessive inherited disorder of copper metabolism due to mutation of the copper transporting gene. The basic strategy of treatment is to reduce the amount of copper in the liver and other tissues by administering both a low copper diet and copper-chelating agents. D-penicillamine is the first choice as a copper-chelating agent. Some serious side effects could occur in 3~5% of all patients following D-penicillamine therapy. We report a 19 year-old male with Wilson's disease who developed nephrotic syndrome 6 months after the initiation of D-penicillamine therapy. Prednisolone was administered to control nephrotic syndrome and D-penicillamine was switched to trientine. Urinary remission was achieved within a week and maintained thereafter. Nephrotic syndrome was proven to be MCNS by kidney biopsy.
Biopsy ; Copper ; Diet ; Hepatolenticular Degeneration* ; Humans ; Kidney ; Liver ; Male ; Metabolism ; Nephrosis, Lipoid* ; Nephrotic Syndrome ; Penicillamine* ; Prednisolone ; Trientine ; Young Adult

Wilson s disease is an autosomal recessive disorder characterized by degenerative changes in the brain, liver, and cornea. Treatment includes D-penicillamine, trientine, and zinc sulfate. D-penicillamine has been used frequently as first line therapy for Wilson s disease. However, nephrotoxicity can occur after D-penicillamine treatment. Among them membranous glomerulopathy is the most common histological abnormality but minimal change lesions have also been reported. Nephrotic syndrome is a late complication of D-penicillamine treatment but very rarely can occur within 2 months after treatment of D-penicillamine. We report the early development of minimal change nephrotic syndrome in a 3-year-old girl with Wilson s disease 3 weeks after initiation of D-penicillamine.
Brain ; Child, Preschool ; Cornea ; Female ; Glomerulonephritis, Membranous ; Humans ; Liver ; Nephrosis, Lipoid* ; Nephrotic Syndrome ; Penicillamine* ; Trientine ; Zinc Sulfate

Wilson disease is an autosomal recessive disorder caused by a deficient ATP7B activity. Copper is an important mineral in the body involved in mitochondrial respiration, melanin biosynthesis, dopamin metabolism, iron homeostasis, antioxidant activity and peptide amidation. Liver is an important organ in copper metabolism related to storing and excretion of bile acids. Copper transport in the liver is a complicated process including different transporter proteins. Generally, Wilson disease shows heterogenous clinical features and symptoms may differ between siblings in a family. This finding suggests that other genes or envrionmental factors may play important roles on determination of disease phenotypes. Clinical symptoms of the disease are mainly related to liver dysfunction and neurologic deterioration. Early diagnosis is important in order to prevent serious complications. Lowered serum ceruloplasmin level and increased urine copper excretion are diagnostic criteria in practice. Histopathologic findings are nonspecific for the diagnosis. Treatment of the disease includes administration of chelating agent such as penicillamine and trientine, dietary restriction of copper, and liver transplantation when chelating agents are not successful.
Bile Acids and Salts ; Ceruloplasmin ; Chelating Agents ; Copper ; Diagnosis ; Early Diagnosis ; Hepatolenticular Degeneration* ; Homeostasis ; Humans ; Iron ; Liver ; Liver Diseases ; Liver Transplantation ; Melanins ; Metabolism ; Penicillamine ; Phenotype ; Respiration ; Siblings ; Trientine

PURPOSE: To investigate the clinical features of long-term follow-up, and the treatment responses in Korean children with Wilson disease(WD). METHODS: The clinical data from ninety-two children with WD, diagnosed at Seoul National University Hospital from 1976 to 1999, were reviewed. Mean duration of follow-up was 5+/-4.5 years. We analysed the patient's records based on the clinical manifestations, laboratory findings, and responses to the treatment. RESULTS: Age of initial presentation was 9.6+/-2.6 years. Mean age of patients who developed neurologic symptoms was 11.6 years. Initial manifestations were characterized as hepatic(70.6%), neurologic(6.5%), and both hepatic and neurologic(10.9%). Kayser-Fleischer(KF) rings were observed in 59 patients(64.1%). All neurologic patients had KF rings. Level of serum ceruloplasmin was low in 91 patients(98.9%). Multiple nodules in the liver and high signal intensity lesions in basal ganglia of the brain were observed on magnetic resonance imaging. Seventy-six patients(82.6%) showed favorable responses to penicillamine(PNC) and the rest of the patients with poor responses were treated with zinc sulfate, trientine, or liver transplantation. Neurologic symptoms improved with PNC in ten out of sixteen patients. However, despite PNC treatment, six patients deteriorated neurologically. Factors affecting the poor response to PNC were associated with the presence of fulminant hepatitis, hemolysis, and KF ring. Ten patients expired due to fulminant hepatitis(9), and hepatocellular carcinoma(1). Most of them died within five months after initial presentations. Ten-year survival rate was 85.4%. CONCLUSION: WD in children begins with various manifestations. PNC is an effective and safe drug to treat WD in most cases. However, the supplementary modalities such as zinc sulfate, trientine and liver transplantation should be considered when the patients show poor responses or adverse reactions to PNC.
Basal Ganglia ; Brain ; Ceruloplasmin ; Child* ; Follow-Up Studies* ; Hemolysis ; Hepatitis ; Hepatolenticular Degeneration* ; Humans ; Liver ; Liver Transplantation ; Magnetic Resonance Imaging ; Neurologic Manifestations ; Penicillamine ; Prognosis ; Seoul ; Survival Rate ; Transplantation ; Trientine ; Zinc ; Zinc Sulfate

D-penicillamine has been reported to cause antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis presenting as rapidly progressive glomerulonephritis or pulmonary-renal syndrome mostly in adults. We report a pediatric case of D-penicillamine induced ANCA-associated vasculitis that manifests as a pulmonary-renal syndrome with a mild renal manifestation. A 13-year-old girl who has been taking D-penicillamine for five years under the diagnosis of Wilson disease visited the emergency room because of hemoptysis and dyspnea. She had diffuse pulmonary hemorrhage, microscopic hematuria, and proteinuria. Myeloperoxidase ANCA was positive, and a renal biopsy revealed pauci-immune crescentic glomerulonephritis. Under the diagnosis of D-penicillamine-induced ANCA-associated vasculitis, D-penicillamine was switched to trientine, and the patient was treated with plasmapheresis, glucocorticoid, cyclophosphamide, and mycophenolate mofetil. Pulmonary hemorrhage improved rapidly followed by the disappearance of the hematuria and proteinuria five months later.
Adolescent ; Adult ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis ; Antibodies, Antineutrophil Cytoplasmic ; Biopsy ; Child ; Cyclophosphamide ; Diagnosis ; Dyspnea ; Emergency Service, Hospital ; Female ; Glomerulonephritis ; Hematuria ; Hemoptysis ; Hemorrhage ; Hepatolenticular Degeneration ; Humans ; Penicillamine ; Peroxidase ; Plasmapheresis ; Proteinuria ; Trientine ; Vasculitis