Medication Summary
Iron depletion, porphyrin reduction, and sclera inflammation control are indicated.
Iron-depleting agents
Class Summary
Iron depletion therapy improves uroporphyrinogen decarboxylase activity, reduces the induction of 5-aminolevulinate synthase, and induces synthesis of porphyrin pathway enzymes in patients who have PCT with normal renal function. Patients with chronic renal failure should be treated further for iron overload resulting from chronic transfusion therapy.
Epoetin alfa (Epogen, Procrit)
Glycoprotein normally produced by the kidneys. Increases RBC production by stimulating division and differentiation of committed erythroid progenitors in bone marrow. Has the identical amino acid sequence to the natural isolate. Manufactured by recombinant DNA technology with same biological effects as endogenous erythropoietin.
Deferoxamine (Desferal)
Freely soluble in water. Approximately 8 mg of iron is bound by 100 mg of deferoxamine. Excreted in urine and bile and gives urine a red discoloration. Readily chelates iron from ferritin and hemosiderin, but not transferrin. Most effective when provided to circulation continuously by infusion. May be administered by SC infusion or bolus, IM injection, or slow IV infusion. Does not effectively chelate other trace metals of nutritional importance.
Provided in vials containing 500 mg of lyophilized sterile drug. 2 mL of sterile water for injection should be added to each vial, bringing the concentration to 250 mg/mL. For IV use, this may be diluted in 0.9% sterile saline, 5% dextrose solution, or Ringer solution. Slow, subcutaneous infusions via a battery-operated pump are the preferred route of administration and can be used at home. Treatment needs to be individualized to patient's symptoms and laboratory values. Long-term therapy slows hepatic iron accumulation and retards progression of hepatic fibrosis.
Ascorbic acid (Vitamin C)
Increases bioavailability of iron by reducing ferric iron to ferrous iron. Blocks degradation of ferritin to hemosiderin.
Porphyrin-reducing agents
Class Summary
Several compounds can chelate or bind porphyrins.
Chloroquine (Aralen)
Binds porphyrins and enhances excretion. Anti-inflammatory activity by suppressing lymphocyte transformation. May have photoprotective effect. Use in porphyria requires very small doses once a week. Larger doses may cause severe hepatic necrosis and death. Reported dosing widely varies and must be titrated to clinical effects.
Cholestyramine (Questran, Prevalite)
Polymeric resin that binds bile acids to form nonabsorbable complex that is excreted unchanged in feces.
Hydroxychloroquine (Plaquenil)
Binds porphyrins and enhances excretion. Inhibits chemotaxis of eosinophils, locomotion of neutrophils, and impairs complement-dependent antigen-antibody reactions.
Cysteine
Amino acid shown to reduce photosensitivity in erythropoietic protoporphyria. May improve elimination of protoporphyrin, but is still under investigation.
Vitamin A
Exact mechanism of action not completely elucidated. Patient must become carotenemic before effects are observed. More than one internal light screen may be responsible for effects. May provide a limited level of photoprotection. Causes yellowing of skin (carotenoderma). Any photoprotection afforded increases slowly after drug is commenced over 4-wk to 6-wk period. When discontinued, skin color and benefit fade over several weeks.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Class Summary
Inflammation of the sclera can be reduced by strong anti-inflammatory medications.
Indomethacin (Indocin)
Rapidly absorbed; metabolism occurs in liver by demethylation, deacetylation, and glucuronide conjugation; inhibits prostaglandin synthesis.
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The heme production pathway. Heme production begins in the mitochondria, proceeds into the cytoplasm, and is then resumed in the mitochondria for the final steps. This figure outlines the enzymes and intermediates involved in the porphyrias. Enzymes names are presented in the boxes. Names of the intermediates are outside the boxes, between arrows. Multiple arrows leading to a box demonstrate that multiple intermediates are required as substrates for the enzyme to produce one product.
Tables
Type of Porphyria |
Age of Onset |
Incidence per 100,000 Population |
Male-to-Female Ratio |
CEP |
Infancy to early childhood; rare in adults |
300 cases total |
1:1 |
PCT |
Type I: Adulthood Type II (heterozygous mutations): Adulthood Type III (homozygous mutations): Childhood |
United States: 4 United Kingdom: 0.05 |
1:1 |
HCP |
Predominantly adulthood Youngest report was child aged 4 y |
Japan: 1.5 Czech: 1.5 Israel: 0.7 Denmark: 0.05 |
1:20 1:4 2:1 1:1 |
VP |
Heterozygous mutation: After puberty Homozygous mutation: Childhood (rare) |
South Africa: 34 |
1:1 |
EPP |
Infancy to childhood |
0.02 |
1:1 |
Porphyria |
Deficient Enzyme |
Location |
Inheritance |
Chromosome Band |
CEP |
Uroporphyrinogen III synthase |
Cytosol |
Autosomal recessive (AR) |
10q25.3-26.3 |
PCT |
Uroporphyrinogen decarboxylase |
Cytosol |
Autosomal dominant (AD) |
1p34 |
HEP |
Uroporphyrinogen decarboxylase |
Cytosol |
AR |
1p34 |
HCP |
Coproporphyrinogen oxidase |
Mitochondrial |
AD |
3q12 |
VP |
Protoporphyrinogen oxidase |
Mitochondrial |
AD |
1q22-23 |
EPP |
Ferrochelatase |
Mitochondrial |
AD, AR |
18q22 |
Porphyrin Type |
CEP |
PCT |
HCP |
VP |
EPP |
Uroporphyrin |
Significantly increased |
Increased |
Within reference range |
Within reference range |
Within reference range |
Coproporphyrin |
Significantly increased |
Increased |
Significantly increased |
Increased |
Within reference range |
Protoporphyrin |
Within reference range |
Within reference range |
Increased |
Significantly increased |
Significantly increased |
Porphyrin type |
CEP and PCT |
HCP and VP |
5-Aminolevulinate |
Within reference range |
Significantly increased |
PBG |
Within reference range |
Significantly increased |
Uroporphyrin |
Significantly increased |
Increased |
Coproporphyrin |
Increased |
Significantly increased |
