A 22-year-old woman is diagnosed with bipolar disorder. Over the next year, she develops neurologic manifestations that include resting and intention tremors, rigidity, chorea, dysphagia, and dysarthria. On physical examination, she has bilateral Babinski signs. There are ring-like deposits of green material involving the cornea bilaterally, but her vision is not decreased. One year later, she has an illness that lasts 3 weeks, with nausea, vomiting, and malaise and scleral icterus. Laboratory findings include serum AST, 100 U/L; ALT, 122 U/L; alkaline phosphatase, 105 U/L; total bilirubin, 4.5 mg/ dL; glucose, 77 mg/dL; and creatinine, 0.9 mg/dL. Serologic test results for hepatitis A, B, and C are negative. This episode subsides without treatment, but she eventually develops cirrhosis. A mutation in a gene encoding for what substance is most likely to be present in this woman?
Wilson disease (hepatolenticular degeneration) with Kayser-Fleischer corneal rings results from a mutation in the gene encoding for a copper-transporting ATPase (ATP7B). Excessive copper deposition occurs, particularly in the liver, putamen, and cornea. Psychiatric and neurologic disturbances are common in Wilson disease, and patients often develop chronic liver disease ranging from acute hepatitis to chronic hepatitis to cirrhosis. In di-antitrypsin deficiency, there can be chronic hepatitis and pulmonary emphysema, but there are no neurologic changes. Cystic fibrosis can lead to pulmonary disease and pancreatic insufficiency. Galactosemia can lead to liver disease and cirrhosis in early childhood. In its most severe form, Gaucher disease from glucocerebrosidase deficiency can lead to neurologic deterioration, but it does not lead to chronic liver disease. Von Gierke disease is a form of glycogen storage disease that does not commonly progress to cirrhosis.
a1-Antitrypsin
CFTR
C Copper-transporting ATPase
Galactose-1-phosphate uridyltransferase
Misc.