Earliest phenotypic manifestation of Idiopathic hereditary hemochromatosis is :
Increased transferrin saturation Elevation in transferrin saturation is the earliest phenotypic manifestation of idiopathic hereditary hemochromatosisQ. Hereditary hemochromatosis is a common inherited single gene disorder. It is characterized by increased intestinal absorption of iron, with deposition of iron in multiple organs. Persons with hereditary hemochromatosis absorb only a few milligrams of iron each day in excess of need. Therefore, clinical manifestations often occur only after 40 years of age, when body iron stores have reached 15-40g (normally, the body stores approximately 4g of iron). In the past hereditary hemochromatosis was usually diagnosed at an advanced stage. The classical description was : ? - Cutaneous hyperpigmentation. - Diabetes mellitus - Cirrhosis Currently, most patients with newly diagnosed hereditary hemochromatosis are asymptomatic i.e., diagnosed at an early state when the patient is still asymptomatic. The shift towards earlier diagnosis is probably the result of including serum iron indices in the diagnosis. Such as : Serum iron - Serum iron binding capacity - % transferrin saturation and serum ferritin These are elevated in hemochromatosis long before the symptoms of hemochromatosis have developed. Therefore serum iron indices are used as screening test for the diagnosis of Heruochromatosis. A.Percent transferrin saturation Percent transferrin saturation is the earliest phenotypic marker of hereditary hemoehromatosisQ. "It is the best screening test used for the diagnosis of hereditary hemochromatosis." Biron binding capacity Now days iron binding capacity is being increasingly used as the screening test for the diagnosis of hereditary hemochromatosis. Many trials have proved that : Iron binding capacity is better than % transferrin saturation as a screening test, but its wide scale use has not been staed till now. C.Serum Ferritin Serum ferritin concentration is usually a good index of body iron stores. Serum ferritin is increased in most untreated patients with hemochromatosis. Asymptomatic or symptomatic family members with the disease have increased serum ferritin. But serum ferritin is not used as screening marker because its act as acute phase reactant and its level is increased in various inflammatory conditions. Besides that its level is also increased in alcoholic liver disease and other hepatocellular injury due to increased release from tissues. Confirmatory testing of hereditary hemochromatosis : Is done by genetic analysis, which is more reliable than determining iron content in liver biopsies. Hereditary hemochromatosis is associated with mutations in the HFE genee. Between 60-93 percent of patients with this disorder are homozygous for mutation designated C282Ye. Liver biopsy is also done to assess if liver fibrosis is present or not.
Post prandial increase in serum iron concentration
Elevated serum ferritin level
Slate grey pigmentation of skin
Increased transferrin saturation