Question: A 52 year old female from Puerto Rico has abnormal ALT, 2 times the upper limit of normal, and the following iron profile: iron 148, TIBC 220, ferritin 750. Other medical conditions include sickle cell disease, obesity and HCV. She is asymptomatic. Which of the following is least likely to explain her current liver test abnormalities?
A. hereditary hemochromatosis
B. sickle cell disease
Answer: It is only natural to think about hereditary hemochromatosis (HH) when we see transferrin saturations > 50% (as above) and elevated ferritins. However, you have to bear in mind this patient’s demographic, a Hispanic from Puerto Rico. Hispanics, Asians and Africans are far less likely to have HH than Caucasians from Celtic and Nordic ancestry.
So, when pretest probability suggests there are other, likely chronic liver diseases, you must think beyond HH. Remember that many chronic liver diseases result in iron dysmetabolism, and the serologic profile fits with iron overload. This includes alcoholic liver disease, HCV, NASH and cirrhosis. This patient is known to have HCV, and her obesity is a major risk factor for NASH.
Having sickle cell anemia suggests that she may have a history of multiple blood transfusions, putting her at risk for secondary iron overload. You cannot distinguish a primary from a secondary iron overload from the iron profile alone. (The histologic distribution of iron is more helpful for that).