A 15-year-old girl comes to the office for follow-up. The patient was diagnosed with Wilson disease a year ago, at which time she began penicillamine therapy. Her dysarthria and academic performance have since improved. Vital signs are normal. Laboratory results are as follows: Which of the following is the most likely explanation for this patient's laboratory findings?

Question

A 15-year-old girl comes to the office for follow-up.  The patient was diagnosed with Wilson disease a year ago, at which time she began penicillamine therapy.  Her dysarthria and academic performance have since improved.  Vital signs are normal.  Laboratory results are as follows:  Which of the following is the most likely explanation for this patient's laboratory findings?

Quizplus · Accepted Answer

Wilson disease is caused by a defective copper transporter within hepatocytes, resulting in copper accumulation in the liver, brain, eye, and other organs. Penicillamine, a first-line therapy for this condition, is a copper-chelating agent that solubilizes copper, which is then excreted in the urine. With initial treatment, urinary excretion of copper is high, as evidenced by this patient's laboratory studies from several months ago. As toxic copper stores diminish with continued chelation, urinary copper excretion decreases (although it remains elevated compared to healthy patients). In addition, although penicillamine can partially reverse liver damage, some patients continue to have mildly elevated transaminases. Nephrotoxicity, which can occur months to years into therapy, is a potential adverse effect of penicillamine and most commonly presents with nephrotic syndrome (ie, proteinuria) due to membranous nephropathy. Pathogenesis is uncertain, but histology findings include diffuse glomerular capillary wall thickening without marked glomerular hypercellularity. (Choices A and B) Noncompliance of penicillamine in patients with Wilson disease results in recurrence of symptoms or worsening liver (eg, cirrhosis) or renal (eg, Fanconi syndrome) manifestations. This patient has improved neurologic symptoms, academic performance, and aminotransferases, making noncompliance unlikely. (Choice D) Interstitial nephritis, a potential adverse effect of any medication, can occasionally cause significant proteinuria. However, hematuria and pyuria would be expected on urinalysis. (Choice E) Although tubular injury (eg, acute tubular necrosis) can result in mild proteinuria, this patient's otherwise normal urinalysis (no granular casts) and lack of risk factors (eg, ischemia, toxin exposure) make tubular injury unlikely. Educational objective: Penicillamine is a copper-chelating agent used as first-line treatment in Wilson disease. Adverse effects include nephrotic syndrome (ie, proteinuria) due to membranous nephropathy. __________ References: Wilson disease. (http://www.ncbi.nlm.nih.gov/pubmed/28723019) Clinical management of Wilson disease. (http://www.ncbi.nlm.nih.gov/pubmed/31179303)

A 15-Year-Old Girl Comes to the Office for Follow-Up