Do Positive Hemochromatosis Studies Make for an Ironclad Diagnosis?

My patient is a 42-year-old man who complains of fatigue. He says that drinkingsome kind of "sports drink" makes him feel better. His complete blood cell count isnormal. His serum ferritin level is 248 ng/mL and his total iron-binding capacity,156 ?g/dL. Aspartate transaminase (AST) level is mildly elevated. Testosteronelevel is normal. Hemochromatosis studies show that he is negative for C282Y butpositive for H63D. Would he benefit from phlebotomy at this point to reduce hisserum ferritin level and iron-binding capacity?---- Subhash C. Sahai, MD
Webster City, Iowa
One frequently encounters patients with elevated serum levels ofiron, transferrin saturation, or ferritin. Many have a liver disorderthat is associated with injury of hepatocytes. These cellscontain iron, ferritin heavy and light chains, and transaminasesthat are released as a result of inflammation or other injury andare detected by serum testing. Common disorders that can cause hepatocyteinjury include nonalcoholic hepatic steatosis or steatohepatitis ("fatty liver"),viral hepatitis (usually hepatitis C), heavy ethanol ingestion, and use of certaindrugs.A few patients with elevated iron, transferrin saturation, or ferritin levelshave iron overload disorders, especially hemochromatosis associated withHFE gene mutations. In these patients, serum iron and transferrin saturationlevels are typically elevated; serum ferritin levels are also elevated in patientswho have iron overload or a coincidental noniron liver disorder.Much less frequently, a clinical picture that resembles hemochromatosisdevelops in older adults with heritable non-HFE iron overload or in those whotake excessive supplemental iron. Regardless of the cause of iron overload, thestorage of much excess iron in the liver causes elevated serum transaminaselevels in some persons.This patient's serum ferritin level is normal for men, which suggests thathe has insufficient iron overload to explain his elevated AST level. Approximately20% of Caucasians in the United States are heterozygous for H63D, andapproximately 4% are homozygous for this mutation; however, iron overloaddoes not develop in most persons with H63D. Fatigue is a nonspecific symptomand does not help with diagnosis or selection of therapy.It is likely that your patient has a liver disorder; hemochromatosis or ironoverload is unlikely. I suggest you review his history for use of drugs, alcohol,and nutritional supplements. You may want to recommend that he undergoliver ultrasound evaluation (to detect fatty liver) and testing for hepatitis B andC antibodies. If his transaminase levels remain elevated and his history, ultrasoundexamination, and blood test results do not reveal the cause, considerpercutaneous liver biopsy. However, a therapeutic trial of phlebotomy seemsunjustified unless increased iron stores are demonstrated by direct examinationof liver tissue.---- James C. Barton, MD
Southern Iron Disorders Center
Clinical Professor of Medicine
University of Alabama
Birmingham