Hemochromatosis

What is the most common sign of Hemochromo

**hepatomegaly 13% might also see: cirrhosis in late disease Right upper quadrant tenderness with hepatomegaly or splenomegaly if cirrhosis present. Signs of fluid overload with congestive heart failure. Sick sinus syndrome with conduction abnormalities.

Prognosis of Hemochrom

-determine hepatic fibrosis or cirrhosis -normal life expectancy with phlebotomy therapy. Early diagnosis and therapeutic phlebotomy to maintain low normal body stores can prevent all known complications of hemochromatosis.

Tx: of Hemochromatosis

-phelbotomy to remove the iron *Weekly therapeutic phlebotomy of 500 mL of whole blood (equivalent to approximately 200-250 mg of iron). Performed until iron-limited erythropoiesis develops -early dx is essential - avoid iron supplements - patient avoid or limit ETOH.

Hemochromatosis

A genetically determined failure to prevent absorption of unneeded dietary iron that is characterized by iron overload and tissue damage --It is the most common inherited liver disease in whites and the most common autosomal recessive genetic disorder.

Follow up with Hemochromo:

Admission to ICU if necessary Coordinated efforts between specialists and primary care practitioner. Regular follow-up visits at least quarterly

Pathophysiology of Hemochromatosis

An adult man loses ~ 1 mg of iron/day. A female (childbearing) loses ~ 2 mg of iron/day. Daily iron intake usually balances at 1-2 mg. Hereditary hemochromatosis is an adult-onset disorder characterized by inappropriately high iron absorption resulting in progressive iron overload.

Is heterozygosity of C28Y considered a true diagnostic of hereditary hemochromatosis.

C282Y heterozygosity not considered diagnostic of hereditary hemochromatosis, but may contribute to iron overload due to other conditions.

Dietary restriction with Hemochromo:

Decrease iron intake - red meats and organ meats. No iron supplements - educate on supplements. Helpful substances: Black & Green tea (tannates). Binds iron. Limit ETOH ingestion, esp. red wines (high in iron). Vitamin C - limit to 500 mg/d -  iron absorption. Don't take concurrently with iron-containing foods.

Alternative Rx treatment of Hemochromatosis

Deferoxamine mesylate (Desferal) - used in primary and secondary iron overload syndromes. Used in patients with hemochromatosis associated with significant anemia or severe end-organ involvement.

Genetic causes of Hemochromatosis

HFE gene C282Y H63D C282Y is the most important. When C282Y is inherited from both parents, iron is absorbed in the intestine from the diet and hemochromatosis can result.

How is iron-limited erythropoiesis develops and phlebotomy is stopped.

Identified by failure of the hemoglobin level and/or hematocrit to recover before the next phlebotomy. It should be continued until transferrin saturation is less than 50% and **serum ferritin levels are less than 50 ng/mL, preferably 20 ng/mL.

Pathology of Hemochromatosis

Results in liver cirrhosis, heart failure, diabetes mellitus, impotence, and arthritis. If untreated, may lead to death from cirrhosis, diabetes, malignant hepatoma, cardiac disease. Mortality is estimated to be 1.7 cases per 10,000 deaths.

When would surgery be considered for hemochromatosis?

Surgical procedures are used to treat 2 important complications: end-stage liver disease and severe arthropathy. After liver transplantation, 1-year and 5-year survival rates are 58% and 42%.

S/S of Hemochromatosis

Symptoms usually begin between age 30 - 50 years. **Intitially present with fatique They may occur much earlier. Clinical manifestations include the following: *Early - Most patients are asymptomatic Severe fatigue (74%) Impotence (45%) Arthralgia (44%) *Late Skin bronzing or hyperpigmentation (70%). Diabetes mellitus (48%). Cirrhosis: the most common cause of death in patients with hereditary hemochromatosis

Labs for Hemochromatosis

Transferrin saturation Initial test of choice but limited. High transferrin saturation=earliest evidence of hemochromatosis. Value greater than 60% in men/50% in women highly specific. Serum ferritin levels elevated higher than 200 mcg/L in premenopausal women and 300 mcg/L in men and postmenopausal women indicate primary iron overload due to hemochromatosis. Especially when associated with high transferrin saturation and evidence of liver disease. Serum Iron: Measuring serum iron has no value in the diagnosis.

Classic triad of Hemochromatosis

cirrhosis, diabetes mellitus, and skin pigmentation occurs late in the disease, when total iron body content is 20 grams (ie, >5-times normal).

Liver Biopsy with Hemochromo:

with determination of hepatic iron concentration and histologic evaluation with iron staining was considered the criterion standard for diagnosis. Now, the diagnosis can be confidently based on genetic testing for the C282Y mutation. Liver biopsy is no longer essential for diagnosis in many cases.