ALAGILLE SYNDROME WITH HEMOCHROMATOSIS

J Leonard, M Borgaonkar

Department of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland

A case report of a patient with both Alagille syndrome and hemochromatosis will be discussed.
Alagille syndrome is a rare inherited condition of arteriohepatic dysplasia usually recognized within the first year of life. Jaundice and cholestasis resulting from biliary tract hypoplasia are the predominant features. Alagille syndrome may result in long-term complications including cirrhosis, hepatocellular carcinoma, and pancreatic insufficiency. Hemochromatosis is also a genetic disorder characterized by increased gut iron absorption. Eventually there can be iron deposition in several areas including the liver, heart, and pancreas leading to organ dysfunction. Until now, there have been no reports of a patient with both Alagille syndrome and hemochromatosis.
A male patient had previously been diagnosed at the age of three with Alagille syndrome. He was jaundiced for the first eight weeks of life and at nine months presented with failure to thrive. He was found to have hepatic dysfunction with elevated alkaline phosphatase and an abnormal lipid profile. As well, a peculiar facies with a prominent forehead was noted. A systolic murmur was found which was later diagnosed as pulmonary artery branch stenosis. At the age of two he presented with diffuse xanthomas. Liver biopsy later confirmed bile duct hypoplasia. He did well after treatment with a low fat diet, phenobarbitol, and cholestyramine. He was referred at the age of 24 for genetic testing after his sister was diagnosed with hemochromatosis. He was found to be homozygous for the C282Y mutation. Serum ferritin was measured at 871ug/L and iron saturation 0.68. Subsequent liver biopsy confirmed increased iron staining in Kuffer cells and hepatocytes but no fibrosis. He began phlebotomy treatment soon after. He has tolerated this well and has developed no complications of hemochromatosis.
This is the first case of a patient with both Alagille syndrome and hemochromatosis. This case represents an interesting association of two genetic disorders. Although almost certainly incidental, this association has never before been reported.