Abstract
Background
Hereditary hemochromatosis is an autosomal recessive disorder where the clinical phenotype of skin pigmentation and organ damage occurs only in homozygotes. Simple heterozygotes, that is, just C282Y, typically do not develop iron overload. Here we present a case where a simple heterozygote in combination with alcoholism developed high ferritin and high transferrin saturation levels indicative of iron overload. Though alcoholism alone could explain her presentation, we hypothesize that an inflammatory cocktail of iron and alcohol probably caused our patient to succumb to acute liver failure at a very young age.
Case presentation
A 29-year-old Caucasian woman presented to the hospital with progressively worsening yellowish discoloration of her eyes and skin associated with anorexia, nausea, vomiting, diffuse abdominal discomfort, increasing abdominal girth, dark urine and pale stools for about 2 weeks. Family history was significant for hereditary hemochromatosis. Her father was a simple heterozygote and her grandmother was homozygous for C282Y. Physical examination showed scleral icterus, distended abdomen with hepatomegaly and mild generalized tenderness. Lab test results showed an elevated white blood cell count, ferritin 539 ng/dL, transferrin saturation 58.23%, elevated liver enzymes, elevated international normalized ratio (INR), low albumin, Alcoholic Liver Disease/Nonalcoholic Fatty Liver Disease (ALD/NAFLD) Index (ANI) of 2.6, suggesting a 93.2% probability of alcoholic liver disease, and phosphatidyl ethanol level of 537ng/ml. Genetic testing showed that the patient was heterozygous for human homeostatic iron regulator protein (HFE) C282Y mutation and the normal allele. Computed tomography (CT) of the abdomen revealed hepatomegaly, portal hypertension and generalized anasarca. Magnetic resonance cholangiopancreatography (MRCP) showed negative results for bile duct pathology. Workup for other causes of liver disease was negative. A diagnosis of acute alcoholic hepatitis was made, with Maddrey’s discriminant function of > 32, so prednisolone was started. Her bilirubin and INR continued to increase despite steroids, and the patient unfortunately died.
Conclusion
Our case highlights the importance of considering hemochromatosis in the differential diagnosis of young patients presenting with liver failure, including cases suggestive of alcoholism as the likely etiology. Larger studies are needed to investigate the role of non-iron factors like alcohol and viral hepatitis in the progression of liver disease in simple heterozygotes with hereditary hemochromatosis, given the high prevalence of this mutation in persons of Northern European descent.
Hemochromatosis and Xeroderma Pigmentosum: Two (Un)Suspicious Neighbors
