Wilson disease—Keeping the bar for diagnosis raised


  • Potential conflict of interest: Nothing to report.

Wilson Disease—Keeping the Bar for Diagnosis Raised

To the Editor:

We read with interest the article by Ala et al.1 regarding the diagnosis of Wilson's Disease in siblings, both of whom were in their eighth decade of life. We recently diagnosed Wilson's Disease in a 60-year-old woman, underscoring the conclusions reached by Ala et al.

This 60-year-old woman was recently referred to us for further evaluation of liver disease. She had no significant past medical history and experienced neither neuro-psychiatric symptoms nor symptoms referable to chronic liver disease. Thus, there was nothing that would warrant further evaluation for Wilson's Disease. An abdominal ultrasound had been obtained to evaluate mild, transient upper abdominal pain and had revealed changes consistent with cirrhosis and portal hypertension. She had essentially normal liver tests, and initial evaluation for causes of chronic liver disease had been negative except for serum ceruloplasmin, which was minimally abnormal. A 24-hour urine copper level was greater that 120 μg/24 hr. She was, therefore, referred to us.

Our evaluation confirmed the lack of neurological features, and ophthalmologic examination did not demonstrate Kayser-Fleischer rings. Serum ceruloplasmin and serum-free copper level were normal. The liver biopsy demonstrated steatohepatitic cirrhosis with a negative rhodanine stain. The hepatic copper was quantified at 1,021 μg/g dry weight. To confirm the diagnosis of Wilson's Disease, we performed fluorescent DNA sequence analysis of the ATP7B gene, which demonstrated compound heterozygosity for the H1069Q mutation and the E1064A mutation, an identical genotype to the patients who presented with neurological manifestations recently described by Ala et al. We initiated therapy with trientine.

Whereas the H1069Q mutation is the most common mutation found in patients with Wilson's disease, the E1064A mutation has only been described once prior to the report by Ala et al.2 In summary, we diagnosed Wilson's Disease in a woman in her seventh decade of life with no symptoms referable to either liver or neuro-psychiatric disease. This finding underscores the conclusion reached by Ala et al. that the diagnosis of Wilson's Disease should be entertained in patients of all ages who present with evidence of liver disease, neurological disease, or psychiatric symptoms.

Roman E. Perri M.D.*, Si Houn Hahn M.D., Ph.D.†, Matthew J. Ferber Ph.D.†, Patrick S. Kamath M.D.*, * Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN, † Department of Laboratory and Medical Pathology, Mayo Clinic College of Medicine, Rochester, MN.