HEMOCHROMATOSIS: AN INCIDENTAL FINDING OF A COMPOUND HETEROZYGOTE C282Y/H63D GENOTYPE
Abstract
Abstract/Introduction. Hemochromatosis (HH), most commonly due to mutations in the HFE gene, is an autosomal recessive disorder. The mutations leads to increased intestinal absorption of iron. Iron overload is defined as transferrin saturation >45% and/or serum ferritin > 200 ng/mL in men and > 150 ng/mL in women. The clinical manifestations of this disease are related to excess iron deposition in tissues including the liver, heart, pancreas, and pituitary. All patients evaluated for iron overload should have C282Y and H63D mutation analysis for diagnosing the presence of HH. (1) C282Y/C282Y genotype confirms diagnosis of HH. (2) C282Y/H63D genotype is compound heterozygote genotype. About 60% of patients have intermediate degree of iron loading, and 35%have normal iron levels. (3) C282Y/wild type genotype is heterozygous for HH. The patients are less risk for iron overload. (4) H63D/wild type or H63D/H63D genotypes is uncertain. Most patients will not have iron overload. Case Presentation. A 54 y/o Caucasian female, with past medical history of migraines and pulmonary embolism of unknown etiology, presented with abdominal pain, nausea and vomiting for 1 day. The pain began in the epigastric region radiating to RUQ and both shoulder blades. It was a pressure like stabbing pain, rated 10/10 on the pain scale. No alleviating or aggravating factors. Patient admitted to similar pain 2 weeks ago, however, it was not as severe and resolved by itself. Both episodes were preceded by steak dinners. Patient admits to non-bloody non bilious emesis, subjective fevers, diaphoresis, abdominal bloating, belching and denies diarrhea. However, she denied any previous abdominal problems including gallbladder and liver. She also denied any recent travel or sick contacts, alcohol, illicit drug or vitamin supplement use. She admits to taking Tylenol/ Advil 1-2 times monthly for occasional migraines. In the ED she was given 1L NS bolus, morphine IV 6 mg x 1, Zofran IV 4 mg x 1, Dilaudid IV 0.5 mg x 1. Hospital Course. Abdominal US revealed increased echogenicity and heterogenous appearance of the pancreas, and hepatomegaly with hepatic steatosis with a normal gallbladder, kidneys, spleen, and no signs of an abdominal aortic aneurysm. CT abdomen revealed an enlarged liver measuring approximately 21 cm and demonstrating steatosis, and cholelithiasis without evidence of cholecystitis was noted. The spleen, pancreas, adrenal glands, stomach, kidneys, urinary bladder, and uterus were within normal limits. CBC was unremarkable. CMP was remarkable for AST/ALT of 760/875 respectively, GGT was 431 with normal alkaline phosphatase, albumin, and lipase. Iron studies revealed ferritin level of 6,875.6, serum iron levels at 210, TIBC of 232 and Iron Saturation at 91%. Evidence of hyperbilirubinemia with a total bilirubin of 1.70 and direct bilirubin at 0.94 was also found. Toxicology screen was positive only for opioid use. Coagulation studies, Hepatitis panel, TORCH panel, HSV1-, HSV-2, and CMV were all negative. GI was consulted for cholelithiasis and a hematology consult was recommended for iron overload.
HEMOCHROMATOSIS: AN INCIDENTAL FINDING OF A COMPOUND HETEROZYGOTE C282Y/H63D GENOTYPE
POSTER PRESENTATIONS
Abstract/Introduction. Hemochromatosis (HH), most commonly due to mutations in the HFE gene, is an autosomal recessive disorder. The mutations leads to increased intestinal absorption of iron. Iron overload is defined as transferrin saturation >45% and/or serum ferritin > 200 ng/mL in men and > 150 ng/mL in women. The clinical manifestations of this disease are related to excess iron deposition in tissues including the liver, heart, pancreas, and pituitary. All patients evaluated for iron overload should have C282Y and H63D mutation analysis for diagnosing the presence of HH. (1) C282Y/C282Y genotype confirms diagnosis of HH. (2) C282Y/H63D genotype is compound heterozygote genotype. About 60% of patients have intermediate degree of iron loading, and 35%have normal iron levels. (3) C282Y/wild type genotype is heterozygous for HH. The patients are less risk for iron overload. (4) H63D/wild type or H63D/H63D genotypes is uncertain. Most patients will not have iron overload. Case Presentation. A 54 y/o Caucasian female, with past medical history of migraines and pulmonary embolism of unknown etiology, presented with abdominal pain, nausea and vomiting for 1 day. The pain began in the epigastric region radiating to RUQ and both shoulder blades. It was a pressure like stabbing pain, rated 10/10 on the pain scale. No alleviating or aggravating factors. Patient admitted to similar pain 2 weeks ago, however, it was not as severe and resolved by itself. Both episodes were preceded by steak dinners. Patient admits to non-bloody non bilious emesis, subjective fevers, diaphoresis, abdominal bloating, belching and denies diarrhea. However, she denied any previous abdominal problems including gallbladder and liver. She also denied any recent travel or sick contacts, alcohol, illicit drug or vitamin supplement use. She admits to taking Tylenol/ Advil 1-2 times monthly for occasional migraines. In the ED she was given 1L NS bolus, morphine IV 6 mg x 1, Zofran IV 4 mg x 1, Dilaudid IV 0.5 mg x 1. Hospital Course. Abdominal US revealed increased echogenicity and heterogenous appearance of the pancreas, and hepatomegaly with hepatic steatosis with a normal gallbladder, kidneys, spleen, and no signs of an abdominal aortic aneurysm. CT abdomen revealed an enlarged liver measuring approximately 21 cm and demonstrating steatosis, and cholelithiasis without evidence of cholecystitis was noted. The spleen, pancreas, adrenal glands, stomach, kidneys, urinary bladder, and uterus were within normal limits. CBC was unremarkable. CMP was remarkable for AST/ALT of 760/875 respectively, GGT was 431 with normal alkaline phosphatase, albumin, and lipase. Iron studies revealed ferritin level of 6,875.6, serum iron levels at 210, TIBC of 232 and Iron Saturation at 91%. Evidence of hyperbilirubinemia with a total bilirubin of 1.70 and direct bilirubin at 0.94 was also found. Toxicology screen was positive only for opioid use. Coagulation studies, Hepatitis panel, TORCH panel, HSV1-, HSV-2, and CMV were all negative. GI was consulted for cholelithiasis and a hematology consult was recommended for iron overload.