| How is pathophysiology of hemochromatosis? | Inborn error in iron metabolism, increased iron absorption from diet, iron overload, eventual fibrosis and organ failure (cirrhosis, cardiomyopathy, DM, hypogonadism) |
| What is hereditary hemochromatosis? | Auto recessive disorder, hemochormatosis gene (HFE) , it is the most common single gene disorder, 1/250-300 white people have it (homozygous), 60-90% of people have homozygous C282Y gene mutation (cysteine to tyrosine substitution), or heterozygous (C282Y/H63D) |
| What is iron overload? | Net absorption of 3-4 mg/day, accumulation of 500-1000 mg iron/year, clinical manifestations occur after age 40 or when stores are 15-40g |
| What are the clinical manifestations of hemochromatosis? | Acc to (age, sex, dietary intake, alcohol, blood loss (menstruation)...)
Alcohol abuse and hepC accelerate it.
Classic description: Cutaneous hyperpigmentation and DM in a pt w/ cirrhosis
We see symptoms of weakness, lethargy, abdominal pain, arthralgia, loss of libido, impotence (and maybe asymptomatic) |
| What are reversible manifestations of hemochromatosis? | Heart (cardiomyopathy, conduction disurbance), liver (abdominal pain, elevated LFTs, hepatomegaly), skin (bronzing (melanin secretion), gray pigmentation (iron deposit)), infection (V.vulnificous, L.mono, P.pseudoTB) |
| What are irreversible manifestations of hemochromatosis? | Liver (cirrhosis/carcinoma -most common cause of death)
Pituitary (GnRH insufficiency->secondary hypogonadism)
Pancreas (DM 30-60%)
Thyroid (hypothyroid)
Genitalia (primary hypogonadism)
Joints (arthropathy (20-70%), pseudogout) |
| How is dx of hemochormatosis? | Labs (serum iron 180-300 micg/dl or 32-54 micmol/dl, transferrin 45-100%, ferritin men 300-3000, women 250-3000)
Liver cytology (iron stain 3+ 4+, iron concentration 3000-30000 micg/g, iron index age>1.9).
Genetic (HFE mutation analysis homo or hetero)
Radiology (CT&MRI not reliable for low iron deposits , newer MRI better sensitivity magnetic susceptibility) |
| What is the treatment of hemochromatosis? | We start tx when we see iron overload/complications, avoid iron supplements, red meat, alcohol, tobacco, handling raw sea food.
Phlebotomy tx (removal of 500 ml blood removes 250mg iron. we do weekly until iron depletion (Hb<120/ ferritin<50/transferrin<50%)
We may need long term maintenance once every 3 months for 2-3 years (to remove >20g) |
| How is algorithm of management of hemochromatosis pt? | . |
| Describe hemochromatosis in women? | 10 X less symptomatic than men, later presentation due to physiologic blood loss in women.
dx same as above, but gold std confirmation by liver biopsy and defines extent of disease
Gene on short arm of chrms 6 not recommended <18 years
Screening done on pt w/chronic liver disease, S&S associated w/hemochromatosis and family hx of iron overload. |
