Porphyrins & Porphyria diagnosis

The porphyrias are caused by deficiencies of enzymes of the heme biosynthetic pathway. This pathway, like other chemical pathways in the body, is a sequence of steps leading to a final product, in this case heme. Heme is essential for life, and each enzyme is also essential, because it is responsible for one of the eight steps in making heme. Each porphyria is due to a deficiency but not a complete absence of one of the enzymes. (Table 1 shows the enzyme that is deficient in each of the porphyrias.)

As in other pathways in the body, each enzyme acts by making a specific change in a chemical called its substrate, to form a product. The product of one enzyme is the substrate for the next. The substrates and products are also known as intermediates in the pathway. When an enzyme is deficient, the substrate for that enzyme may accumulate. (Table 1 also shows the substrates and products of the heme pathway with the sequence indicated by arrows.)

In the porphyrias, large amounts of intermediates can accumulate in the body, especially when the conditions are active. These intermediates include porphyrin precursors (delta-aminolevulinic acid and porphobilinogen) and porphyrins. Depending on the type of Porphyria, the excess intermediates are produced and accumulate first in the liver or the bone marrow and then appear in blood. They are excreted from the body in urine and feces. Some of the intermediates undergo changes after they leave cells in the liver and bone marrow and before they are excreted from the body (Table 1).

The most common and useful tests measure porphyrin precursors and porphyrins in blood (plasma and red blood cells), urine or feces. Which intermediates accumulate depends on the type of Porphyria. When Porphyria is active, the amounts that accumulate are very large. This enables a diagnosis of active Porphyria to be made quite readily.