Porphyria results from an enzymatic defect in the heme biosynthetic pathway that results in excess accumulation and excretion of porphyrins or porphyrin precursor. Tefferi et al developed a simple algorithm for evaluating patients with possible porphyria. The work was done at the Mayo Clinic.
Porphyrin intermediates in first half of heme biosynthetic pathway:
(1) porphobilinogen (PBG), delta aminolevulinic acid (ALA), uroporphyrin
(2) water soluble and fat insoluble
(3) excreted in the urine
Porphyrin intermediates in second half of heme biosynthetic pathway:
(1) coproporphyrin and protoporphyrin
(2) fat soluble
(3) excreted via the bile into the feces
(4) coproporphyrin also water soluble and is excreted in the urine
Testing:
(1) 24 hour urine for porphobilinogen and delta-aminolevulinic acid
(1a) some laboratories prefer no preservatives
(1b) some laboratories specify separate specimens for PBG and ALA, with PBG collected with sodium bicarbonate and ALA collected with hydrochloric acid
(2) 24 hours stool collection for stool porphyrins
Algorithm for Interpreting Studies (Tefferi, Figure 2, page 290)
If urinary ALA and PBG are not increased during an attack, then the patient does not have acute porphyria.
If urinary ALA and PBG are not increased in the interval between attacks, the patient could have neurocutaneous porphyria.
(1) If stool porphyrins are normal, then the person does not have acute porphyria.
(2) If the stool shows elevated protoporphyrins, then the patient has variegate porphyria.
(3) If the stool shows elevated coproporphyrins, then the patient has hereditary coproporphyria.
If urinary ALA and/or PBG are increased between attacks or during an attack, then the person could have neuro- or neurocutaneous porphyria.
(1) If stool porphyrins are normal, then the person has acute intermittent porphyria.
(2) If the stool shows elevated protoporphyrins, then the patient has variegate porphyria.
(3) If the stool shows elevated coproporphyrins, then the patient has hereditary coproporphyria.
Limitations:
• The algorithm assumes that changes in porphyrin excretion is due to a hereditary porphyria.
• Lead poisoning may result in excretion of ALA greater than PBG, with increased stool porphyrins.
• Hereditary tyrosinemia may result in increased excretion of ALA in the urine.
• Liver disease and alcoholism may result in increased coproporphyrin excretion.
• Oral contraceptives may result in increased PBG excretion.
• Protoporphyria is not detected by the algorithm. This requires testing for free erythrocyte protoporphyrins.
