Hemoglobinopathies are rare, inherited disorders caused by mutations of the globin genes.

Epidemiology

• Incidence - rare
• Age - neonatal; usually not in the first few months (protected by fetal hemoglobin)

Genetics

• More than 30 mutations exist
• Inherited as autosomal dominant disorders, although spontaneous mutations occur

Pathophysiology

• Unstable hemoglobins exhibit altered solubility due to oxidation of amino acid residues in globin chains
  • Leads to weakened binding of heme to globin preventing formation of intact hemoglobin tetramer
  • Only tetramer can remain dissolved in circulating red blood cells (RBCs)
    • Mutants cannot remain dissolved
    • Leads to hemoglobin precipitation
  • Heinz body is precipitate of undissolved components of globin chains and heme
    • Attach to RBC membranes and trigger spleen to further damage RBCs
    • End result is premature destruction of RBCs with hemolysis and eventual anemia

Clinical Presentation

• Congenital Heinz body hemolytic anemia
• Jaundice, anemia, dark urine, leg ulcers, bilirubin gallstones
• Neonatal syndromes
  • Hemoglobin Poole and Hemoglobin Hasharon
  • Neonatal hemolysis - jaundice, anemia
  • Resolves with aging as adult hemoglobin replaces fetal hemoglobin

Diagnosis

• Laboratory testing
  • Heinz bodies variably present on peripheral blood smear
    • Provocative testing using isopropanol instability test will unmask precipitation and make diagnosis easier
  • Hemoglobin electrophoresis may show an abnormal band of precipitated heme and globin
    • Some mutants not detectable by electrophoresis or are too unstable