Gastrointestinal

Question 1

Wilson Disease

Answer 1

Also called hepatolenticular degeneration. Autosomal recessive mutations in hepatocyte copper-transporting ATPase (ATP7B gene; chromosome 13) -> decreased copper incorporation into apoceruloplasmin and excretion in bile -> decrease serum ceruloplasmin. Copper accumulated, especially in liver, brain, cornea, kidneys; increase urine copper.
Presents before age 40 with liver disease (eg, hepatitis, acute liver failure, cirrhosis), neurologic disease (eg, dysarthria, dystonia, tremor, parkinsonism), psychiatric disease, Kayser-Fleischer rings (deposits in Descemet membrane of cornea), hemolytic anemia, renal disease (eg, Fanconi syndrome).
Treatment: chelation with penicillamine trientine, oral zinc. Liver transplant in acute liver failure related to Wilson disease.

Question 2

Hemochromatosis

Answer 2

Autosomal recessive. On HFE gene, located on chromosome 6; associated with HLA-A3. Leads to abnormal iron sensing and increased intestinal absorption. Iron overload can also be secondary to chronic transfusion therapy.
Iron accumulates, especially in liver, pancreas, skin, heart, pituitary, joints. Hemosiderin can be identified on liver MRI or biopsy with Prussian blue stain.
Presents after age 40 when total body iron >20g; iron loss through through menstruation slows progression in women. Classic triad of cirrhosis, diabetes mellitus, skin pigmentation. Also causes restrictive cardiomyopathy (classic) or dilated cardiomyopathy (reversible), hypogonadism, arthropathy (calcium pyrophosphate deposition; especially metacarpophalangeal joints). HCC is common cause of death.
Treatment: repeated phlebotomy, iron chelation with deferasirox, deferoxamione, deferiprone.