Liver Dysfunction and Steatosis in Familial Hypobetalipoproteinemia

A 32-year-old man presented with increases in serum alanine aminotransferase activity, iron concentration, and transferrin saturation, suggestive of hepatic dysfunction and iron overload. In addition, he had unusually low plasma concentrations of LDL-cholesterol and apolipoprotein (apo) B. Hepatic ultrasonography was consistent with fatty liver. On liver biopsy, I marked steatosis and moderate to marked iron deposition were observed. The patient was found to carry the HFE C282Y and H63D mutations, which are associated with hereditary hemochromatosis, and the alpha(1)-antitrypsin PiZ variant. An immunoblot of plasma for apoB showed the presence of a truncated apoB species, indicative of familial hypobetalipoproteinemia. DNA sequence analysis revealed that the patient was heterozygous for the apoB-80.5(c.11040T>G) mutation. This unique case shows an unusual combination of underlying disorders that could all be contributing to liver dysfunction and fatty liver. (C) 2005 American Association for Clinical Chemistry.