Primary / Idiopathic Hemochromatosis

= autosomal recessive genetic disorder (abnormal iron-loading gene on short arm of chromosome 6) in thalassemia, sideroblastic anemia

Defect: increased absorption + parenchymal accumulation of dietary iron

Organs: liver, pancreas, heart (parenchymal iron overload)

Homozygous frequency: 1÷200; M÷F = 1÷1

Age:>30 years (M), usually after menopause (F);

◊Females protected by menstruation

• cirrhosis (frequently present at time of diagnosis)
• “bronzed diabetes” (50%) = insulin-dependent diabetes ← excess intracellular iron reduces function of beta islet cells while reserve capacity of exocrine function is not exceeded by toxic effects of iron; skin pigmentation
• congestive cardiomyopathy ← myocardial muscle accumulates toxic levels of intracellular iron
• hypogonadism + decreased libido ← pituitary dysfunction
• slowly progressive arthritic symptoms (30%)
• increased serum iron + ferritin level (nonspecific)
• transferrin saturation + serum ferritin assay (specific)
• Skeleton
  Distribution: most commonly in hands (metacarpal heads, particularly 2^nd + 3^rd MCP joints), carpal (30–50%) + proximal interphalangeal joints, knees, hips, elbows
  • generalized osteoporosis
  • small subchondral cystlike rarefactions with fine rim of sclerosis (metacarpal heads)
  • arthropathy in 50% (iron deposition in synovium)
  • uniform symmetric joint space narrowing (unusual for degenerative joint disease)
  • enlargement of metacarpal heads:
    • hook-like osteophytes on radial aspect of metacarpal heads (CHARACTERISTIC)
  • chondrocalcinosis in >60%, knees most commonly affected
    1. calcium pyrophosphate deposition ← inhibition of pyrophosphatase enzyme within cartilage which hydrolyzes pyrophosphate to soluble orthophosphate
    2. calcification of triangular cartilage of wrist, menisci, annulus fibrosus, ligamentum flavum, symphysis pubis, Achilles tendon, plantar fascia
• Brain
  • marked loss in SI of anterior lobe of pituitary gland ← iron deposition
• Abdomen
  • decreased T2 signal intensity in liver, pancreas
  • normal SI of spleen on T2WI + T2*WI

Dx: liver biopsy with hepatic iron index >2 (= iron concentration in µmol/g of dry weight divided by patient's age in years)

Cx: hepatoma in 14% (iron stimulates growth of neoplasms)

Prognosis: death from CHF (30%), death from hepatic failure (25%), death from HCC (in up to 33%)

Rx:

1. Phlebotomy (returns life expectancy to normal if instituted prior to complications)
2. Screening of family members (gene can be located by human leukocyte antigen typing)

DDx:

1. Pseudogout (no arthropathy)
2. Psoriatic arthritis (skin + nail changes)
3. Osteoarthritis (predominantly distal joints in hands)
4. Rheumatoid arthritis
5. Gout (may also have chondrocalcinosis)