Last updated: March 31, 2015
ICD-9 Code: 275.0.
Definition: Hemochromatosis is a common hereditary disorder of excessive iron absorption and deposition causing tissue damage and organ dysfunction.
Etiology: Hemochromatosis is an autosomal recessive condition related to mutations in HFE, a gene located on the short arm of chromosome 6 that has homology to major histocompatibility complex class I molecules. HFE encodes a 348-amino-acid protein, known as the hereditary hemochromatosis protein, that functions in conjunction with 132-microglobulin to regulate intestinal iron uptake. The disease has age-related incomplete penetrance and varied clinical expression. The defect causes increased intestinal absorption of iron, resulting in increased saturation of serum transferrin, elevated serum ferritin concentrations, and deposition in the liver, heart, some endocrine organs, and joints. Heterozygotes have increased iron stores but rarely develop clinical disease.
Demographics: Although present from birth, the peak age at symptom onset is 40 to 60 years. The female:male ratio is 1:5. Prevalence is 30 to 60/10,000. It is mostly seen in northern European populations; 10% of whites are heterozygous for the mutation.
Cardinal Findings: Multiple organ systems may be affected. The classic triad of liver cirrhosis, skin hyperpigmentation and diabetes (bronze diabetes) is rare.
—Liver: Transaminases are elevated, with occasional hepatomegaly and tenderness and eventual cirrhosis.
—Endocrine: Diabetes is usually a late manifestation. Hypogonadism (loss of libido, impotence, testicular atrophy, gynecomastia) and skin pigmentation (related to increased melanin) are often seen.
—Heart: Cardiac involvement is uncommon but may present as a cardiomyopathy.
—Arthropathy: This may be a presenting feature. Joints typically involved include the second and third metacarpophalangeal and proximal interphalangeal joints, hips, knees, ankles and spine. Iron deposition may cause pseudogout. Joints presentations mimic either pseudogout, OA or RA-like synovitis.
Diagnostic Tests: Screen with transferrin saturation (100 X serum iron/total iron binding capacity); if >50%, measure serum ferritin; in hemochromatosis, serum ferritin exceeds 200 ng/mL in males and 100 ng/mL in females. Ferritin behaves as an acute-phase reactant and levels may increase in the presence of inflammatory disease elsewhere. Diagnosis may be confirmed with liver biopsy, but in many with classic clinical features, testing for the C282Y homozygous mutation in the HFE gene may suffice.
Imaging: Half will have radiographic chondrocalcinosis. Typical degenerative findings include joint space narrowing, sclerosis and hook osteophytes. of Noninvasive imaging with CT or MRI may be useful. Screen first-degree relatives because early detection and treatment can prevent clinical disease.
Keys to Diagnosis: Consider hemochromatosis in all cases of transaminitis and chondrocalcinosis and when an OA-like disease (especially in MCP2 & MCP3 joints) is seen in men in their fourth and fifth decade.
Therapy: Weekly phlebotomy is performed to deplete iron stores; maintenance phlebotomy should occur three to six times per year to keep the hematocrit <40%. The arthropathy is usually not reversible. Arthritis should be treated symptomatically.
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