Drug-associated nephrotic syndrome in a child with Wilson's disease

BACKGROUND: Wilson's disease (WD) (synonyms: Wilson–Konovalov disease, hepatolenticular degeneration, hepatocerebral dystrophy) is a rare, severe, hereditary multisystem disorder that manifests itself primarily in liver, neurological, and psychiatric disorders due to excessive copper deposition in organs and tissues. The long latent course and polymorphism of clinical symptoms make diagnostics difficult. WD manifests itself in childhood, adolescence, and later in life. WD diagnostics is based on a combination of clinical symptoms, laboratory test data (determination of ceruloplasmin levels in the blood, copper excretion in the urine), and molecular genetic testing.

Complex treatment of WD primarily involves adherence to a copper-eliminating diet. A mandatory condition for the effectiveness of treatment of patients with WD is lifelong chelation therapy. The drug of choice in all age groups is penicillamine (a penicillin derivative), which has a significant number of side effects. Adverse reactions against the background of penicillamine therapy develop in about 30% of cases. These include changes in the nervous system (loss of taste, pyridoxine-deficiency polyneuritis), respiratory system (interstitial pneumonitis, diffuse fibrosing alveolitis, Goodpasture's syndrome), digestive system (decreased appetite, nausea, vomiting, diarrhea, aphthous stomatitis, glossitis, intrahepatic cholestasis, pancreatitis), kidneys (nephritis, nephrotic syndrome, hematuria).

CLINICAL CASE DESCRIPTION: The case history of a 6-year-old girl with WD is analyzed. The peculiarity of the clinical case presented by us is the latent course of the disease, which was suspected when cytolysis syndrome was detected in connection with an examination for episodic abdominal pain. Further examination showed a decrease in the concentration of ceruloplasmin, initially borderline values of copper excretion in urine, and questionable values in the penicillamine test. Molecular genetic testing was important for establishing the diagnosis, and confirming the diagnosis. Prescribed chelation therapy with penicillamine led to the normalization of cytolysis syndrome parameters, but caused serious adverse events in the form of nephrotic syndrome, which required replacing penicillamine with trientine and prescribing glucocorticoids. Against the background of treatment correction, stable clinical and laboratory remission of nephrotic syndrome was achieved with satisfactory renal and liver function parameters and no manifestations of cytolysis.

CONCLUSION: A moderate increase in biochemical markers of cytolysis, cholestasis, and bilirubin concentration, refractory to standard treatment, requires in-depth examination, including molecular genetics, to exclude WD. If side effects of penicillamine derivatives are detected, immediate correction of pathogenetic therapy with replacement of the chelating drug is necessary.