Hemochromatosis

Question 1

Screening for HC

Answer 1

1st degree relatives with HFE mutation –> genetic testing
Otherwise:
Patients with symptoms/signs that may be explained with iron overload
Patients with persistently elevated serum ferritin not explained by underlying inflammatory/systemic disease
Do fasting trasferrin/iron stauration

If >0.6 or two results of >0.45, genetic testing for European decent, non-European:referral

Question 2

Early stages of hemochromatosis

Answer 2

Most commonly:
fatigue, weakness, weight loss, abdominal pain, arthalgia

may also experience: arthritis, symptoms of gonadal failure, SOB/dyspnea

Question 3

Advanced stages of hemochromatosis

Answer 3

Arthritis
abnormal liver function
glucose intolerance, diabetes
chronic abdominal pain
severe fatigue
hypopituitarism
hypogonadism
cardiomyopathy and arrhythmia
cirrhosis
lievr cancer
heart failure
gray/bronze skin pigmentation

Question 4

Pros for hemochromatosis population screening

Answer 4

Common
Associated morbidity & mortality
sensitive screening tests
effective treatment
individuals identified precirrhotic: survival rate equal to average population

Question 5

Cons for hemochromatosis population screening

Answer 5

relationship between genotype and clinical phenotype is unclear
concerns about how best to accomplish the screening, at what age, whether it should be for gen population or targeted “high risk” populations, what the test would be, and social/ethical issues

Question 6

Defects in hemochromatosis

Answer 6

Hepcidin deficiency, especially those associated with missense mutations in genes that encode HFE

HFE gene product interacts with transferrin receptors –> thought to help regulate the amount of iron that is sensed by liver cells