How Effective is Zinc Therapy for Wilson’s Disease?

A study from France (R Santiago et al. JPGN 2015; 61: 613-18) examined the use of zinc therapy for Wilson’s disease. Though the national survey had 90 children from 6 centers, there were only 26 who were treated with zinc and only 9 who had received zinc as a first-line single therapy.

Despite the small numbers, data on treating children with Wilson’s disease are fairly sparse; as such, this article provides some helpful information.

The study reviews zinc’s mechanism of action:

“Oral zinc induces enterocyte synthesis of metallothionein, a cystic-rich protein acting as an endogenous chelator for metals, which preferentially binds copper in the enterocyte and inhibits its entry into the portal circulation. Thereby, it reduces copper intestinal absorption and leads to copper elimination in fecal contents within senescent enterocytes.”

Key results:

  • “Median transaminase level normalized within 6 months from treatment initiation” in the entire cohort of 26 children.  However, 10 of 26 children had abnormal ALT at 6 months into therapy.
  • Zinc dose was gradually increased such that 38% eventually had doses “exceeding recommended doses” which were >75 mg/day in 6-15 years and >150 mg/day in those ≥16 years.
  • Overall, the authors thought that zinc appeared to be less effective.  Failure with zinc occurred in 5 of 9 (3 due to ineffectiveness, 2 due to poor adherence).  The authors note that decompensation has been reported in children and adults on zinc monotherapy.

The authors indicate that zinc therapy is likely most appropriate after an induction phase with chelators in most children.  Criteria for changing to zinc include the following: “patients should be clinically well…with normal transaminase levels and hepatic synthetic function, non-ceruloplasmin-bound copper concentration within the normal range, and 24-hour urinary copper excretion in the range of 200-500 mcg/24 h.”

Additional precautions with zinc acetate (which is often better tolerated than chelators), 4 of 26 children in this study had gastric irritation, including one child with a perforation.  Therefore, a low threshold for endoscopy should be set in a child with epigastric pain. Adherence can be problematic due to the timing & frequency (TID) of zinc administration.  Monitoring urinary zinc excretion can be useful to monitor compliance.

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