A 21-year-old man comes to the office with impaired balance, tremor, and difficulty speaking. His symptoms have developed slowly over the last several months. The patient is found to have elevated serum transaminases. Viral hepatitis serologies are negative. He does not use tobacco, alcohol, or illicit drugs. He has a sibling who was diagnosed at a young age with a progressive neurologic disease. Which of the following diagnostic studies would be the most helpful for confirming the diagnosis in this patient?

Question

A 21-year-old man comes to the office with impaired balance, tremor, and difficulty speaking.  His symptoms have developed slowly over the last several months.  The patient is found to have elevated serum transaminases.  Viral hepatitis serologies are negative.  He does not use tobacco, alcohol, or illicit drugs.  He has a sibling who was diagnosed at a young age with a progressive neurologic disease.  Which of the following diagnostic studies would be the most helpful for confirming the diagnosis in this patient?

Quizplus · Accepted Answer

11ec160b_39e9_aed9_9249_d152e21f5b84_MD0001_00 Wilson disease is a rare, autosomal recessive disorder most often identified in individuals age 5-40. A mutation of gene ATP7B hinders intracellular hepatocyte copper transport, causing reduced formation/secretion of ceruloplasmin (the major extracellular copper transport protein) and decreased secretion of copper into the biliary system. Copper is a pro-oxidant and causes hepatocellular injury by producing free radicals. Eventually, copper leaks from injured hepatocytes into the blood to be deposited in various tissues (eg, basal ganglia, cornea). Neurologic involvement can result in movement abnormalities and psychiatric symptoms. Almost all patients with neuropsychiatric disease have Kayser-Fleischer rings (green/brown copper deposits in the Descemet membrane of the cornea), which can be detected on slit lamp examination if not seen on visual inspection. The diagnosis can be confirmed by the presence of low serum ceruloplasmin, increased urinary copper excretion, and elevated hepatic copper content on liver biopsy. (Choice A) Anti-smooth muscle antibodies are associated with autoimmune hepatitis. Although serum transaminases can be elevated, neurologic symptoms are not characteristic. (Choice B) Genetic testing for triplet repeat expansions may be considered in patients with suspected Friedreich ataxia, an autosomal recessive disorder that typically presents during adolescence with neurologic dysfunction (eg, limb/gait ataxia, dysarthria) and hypertrophic cardiomyopathy. (Choice C) Although atrophy/cavitation of the basal ganglia may be identified on brain MRI in patients with advanced Wilson disease, these findings are not specific and therefore are not used to confirm the diagnosis. Neuroimaging can be useful in excluding other causes of movement disorder (eg, tumor, infarction, demyelinating disease). (Choice D) Alpha-1 antitrypsin deficiency is an autosomal codominant disorder that usually presents with early onset (age <45), panacinar emphysema, and liver disease. (Choice E) Elevated serum ferritin and transferrin saturation is characteristic of hemochromatosis, an autosomal recessive disorder associated with increased intestinal iron absorption. Patients typically present with liver disease, skin pigmentation, diabetes mellitus, and cardiac enlargement due to excessive iron deposition into tissues. Educational objective: Wilson disease is an autosomal recessive condition characterized by excessive copper deposition into tissues (eg, liver, basal ganglia, cornea). It typically presents in young adults with liver disease, neuropsychiatric symptoms (eg, gait disturbance, dysarthria, depression, personality changes), and Kayser-Fleischer rings on slit lamp examination. __________ References: Wilson disease. (http://www.ncbi.nlm.nih.gov/pubmed/20955957)

A 21-Year-Old Man Comes to the Office with Impaired Balance