A 61 year-old-man with type 2 diabetes mellitus and progressive forgetfulness was admitted to the hospital with generalized weakness and difficulty ambulating for one week. His review of systems was positive for hyperpigmentation over the past year. He was taking aspirin, insulin and lisinopril. He was a chronic smoker. Family history was unremarkable. On initial examination, his vital signs were within normal limits. He was sleepy but easily arousable, and had intermittent myoclonic jerking. His mini-mental examination score was 20/30. Kayser Fleischer rings were absent on funduscopic examination. His gait was unstable but Romberg sign was negative. Cardiovascular and respiratory exams were unremarkable. Complete blood count was remarkable for thrombocytopenia (69,000/ul) and comprehensive metabolic panel showed total bilirubin of 1.2 mg/dl, AST-78 U/L, ALT-61 U/L, and albumin of 2.8 mg/dl. A computed tomography (CT) scan of brain without contrast was unremarkable. Further work up was requested to evaluate for early onset dementia and acute encephalopathy including TSH, HIV screen, RPR, acute hepatitis panel, vitamin B12, and vitamin B1, which were unremarkable. Magnetic resonance imaging of the brain could not be obtained because patient had a spinal stimulator. On day 2, his mental status continued to deteriorate. Further labs were ordered which were significant for ammonia of 111 mcmol/L (normal<32 mcmol/L), INR of 1.4, and a serum ferritin was 5911 ng/ml (normal, 8-388 ng/ml), and transferrin saturation of 74%. A diagnosis of hemochromatosis was made. A CT abdomen showed the liver with irregular contour and increased density consistent with cirrhosis. Genetic testing for hemochromatosis was positive for the C282Y mutation on HFE gene.
Hemochromatosis is a relatively rare autosomal recessive disorder. Advances in genetic testing have resulted in earlier diagnosis of hemochromatosis, and the classic triad of skin pigmentation, diabetes mellitus and cirrhosis is rarely seen. Encephalopathy is a frequent reason for hospitalization and has a broad differential diagnosis. Our patient presented with acute encephalopathy as an advanced symptom of hemochromatosis from underlying liver cirrhosis. Early diagnosis and institution of therapy is vital in the management of advanced hemochromatosis and can potentially be life-saving.
A history of diabetes and transaminitis in patients with altered mental status should raise the suspicion of hemochromatosis. Moreover, hyperpigmentation in hemochromatosis develops over many years, and patient and family members may not consider it as a symptom.