Chapter 12: Hemochromatosis

Presentation: Affected individuals typically present what age? __________ accumulation over time leads to what? What is common? MC in males or females? Due to what?

•Affected individuals typically present in 40's. •Iron accumulation over time leads to liver cirrhosis and other organ failure. •Asymptomatic disease is common. -Males MC due to regular blood loss during menstruation (referred to as sex-influenced phenotype). *-Sex influenced phenotype pictured**

treatment? What agents that do what? What type of management? What transplant?

•Chelating agents that bind to iron and prevent its use or deposition in the body are rarely used due to the efficacy of phlebotomy •Dietary management should include avoidance of iron containing supplements, limited foods high in iron, and avoidance of excessive amounts of vitamin C which increases absorption of dietary iron •Liver transplant is the only treatment for patients with end-stage liver disease

Liver cirrhosis: caused by what? Is a what type of risk factor for development of what? While _________ can be performed, ___________ has replaced it? What is recommended for patients with cirrhosis to evaluate hepatic cancer? Most sensitive technique?

•Cirrhosis, which may be caused by hemochromatosis, is an independent risk factor for the development of hepatocellular carcinoma. •While liver biopsy can be performed to confirm a diagnosis of HH or to diagnose cirrhosis and/or hepatocellular carcinoma, imaging and genetic testing have largely replaced it. •Ultrasound is recommended for patients with cirrhosis to evaluate for hepatic cancers. However, MRI is the most sensitive technique.

Chapter summary:

•HHC caused by point mutation in the HFE gene and is inherited in a autosomal recessive pattern •Incidence of 1 in 200 Caucasians in the U.S. •Males manifest more symptoms than females due to menstruation •Mutations result in increased iron absorption and cause increased iron stores in liver, pancreas, skin and heart. •Common symptoms include abdominal pain, fatigue and arthralgias. •Advanced disease manifests as hepatomegaly, hepatic cirrhosis, hepatocellular carcinoma, diabetes mellitus, cardiomyopathy, hypogonadism, arthritis, and hyperpigmented skin. •Serum ferritin and transferrin saturation have the greatest sensitivity and specificity as biomarkers. •Persons with cirrhosis have an increased risk of hepatocellular carcinoma •Therapeutic phlebotomy is the treatment of choice.

Diagnosis: Lab studied include what? (4) Elevated what levels are earliest phenotypic manifestation?

•Laboratory studies include: -Serum iron- normal to increased -Serum ferritin- increased -TIBC- normal to decreased -Serum transferrin saturation- increased -Elevated transferrin saturation levels are typically the earliest phenotypic manifestation of HH, preceding clinical manifestations of the disease.

Hyperpigmentation results from combination of what? Hemochromatosis was previously referred to as what? Due to what?

•Results from a combination of iron deposits in the skin and increased melanin. •Hemochromatosis was previously referred to as "bronze diabetes (PICTURED)" due to the common occurrence of insulin resistance and darkened skin.

Expected Serum Iron Values in HHC: Serum iron? Serum ferritin? TIBC? Serum transferrin? Increased or decreased???

•Serum Iron----------------Normal to Increased •Serum Ferritin------------------------Increased •TIBC------------------------Normal to Decreased •Serum transferrin saturation-----------Increased

testing: Wide availability of what eliminated need for liver biopsy? Testing is performed using what? While most individuals are what and do not develop what they may have what? B/c sx do not develop til when? It is reasonable to screen who? What screening is not recommended?

•The wide availability of HFE gene testing has largely eliminated the need for liver biopsy. •Testing is performed using polymerase chain reaction (PCR) using a whole blood sample. •While most individuals are heterozygous for the HFE mutation and do not develop the disease, they may have abnormal test results. •Because symptoms of hemochromatosis do not develop until later in life, it is important to identify those at risk for iron over-load. •It is reasonable to screen all adult patients with any family history of iron overload or signs and symptoms of hemochromatosis. •Pediatric screening is not recommended.

Associated sx?

•Type 2 HH •Type 3 HH •Type 4 HH •African (Bantu) iron overload •Neonatal Hemochromatosis •Secondary Iron overload syndromes

Presentation: Typically present with what? Other findings may include what? Less common findings include what?

•Typically present with non- specific complaints such as abdominal pain, arthralgia, and fatigue. •Other findings may include abnormal liver function tests, diabetes, and hyperpigmentation of the skin. •Less common findings include hepatomegaly, heart murmurs, conduction disturbance on EKG, hypothyroidism, hypogonadism, and arthritis.