Hemochromatosis is inherited as an autosomal recessive disorder that is relatively common in White Americans. About 10% of White Americans carrying the gene, but most are heterozygotes. Homozygotes are infrequent (about 0.3-0.5% of Americans). Transferrin saturation is the recommended screening test for hemochromatosis.
Specimen: Random serum sample.
Heterozygotes show a transferrin saturation of 50 - 62%.
Homozygotes show a transferrin saturation usually from 70 - 99% but may show lower levels overlapping with heterozygote levels
Serum ferritin and iron are typically elevated in hemochromatosis, but may be elevated in other conditions.
(1) The upper limit of reference range for serum ferritin in adult males is 250 ng/mL.
(2) The upper limit in adult females is 120 ng/mL if premonpausal and 263 ng/mL if postmenopausal.
(3) Glenn (1996) uses decision levels of 400 ng/mL for men and postmenopausal women and 200 ng/mL in younger women.
(4) Ferritin is an acute phase reactant which may be elevated in many conditions, especially chronic inflammatory disorders.
Algorithm for screening and treating hemochromatosis
(1) If the transferrin saturation is elevated ( > 60% in males, > 50% in females):
(1a) retest patient after overnight fast
(1b) if repeat test is elevated, measure serum ferritin.
(2) If the serum ferritin is greater than normal for patient's age and sex, then attempt to obtain a liver biopsy to measure hepatic iron for disease confirmation.
(2a) Initiate a phlebotomy program with frequent phlebotomies (initially every week) to reduce serum ferritin.
(2b) Phlebotomy continued lifelong.
(2c) Serum ferritin is measured each year, and amount phlebotomized is adjusted to maintain ferritin within the normal reference range.
(3) If the serum ferritin is normal for patient's age and sex:
(3a) Option (a): Repeat ferritin testing every 2 years, and initiate phlebotomy if the ferritin increases above normal for age and sex.
(3b) Option (b): Initiate a phlebotomy regimen of 3-4 units per year. Measure ferritin every 2 years and adjust frequency of phlebotomy to keep ferritin within the normal reference range.
(4) If serum transferrin and ferritin levels are both within decision levels on two occasions, then the likelihood of hereditary hemochromatosis is very low.
