Diagnosis of Porphyria

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Blood, urine, and stool tests, or genetic testing all are used by clinicians in making a diagnosis of porphyria.

Porphyrias are a group of genetic disorders caused by disruptions in the production of heme, a necessary molecule for transporting oxygen in living cells.

Heme consists of iron and protoporphyrin IX, and is built step-wise out of other porphyrins (chemicals in the body) and precursor molecules.

Disruptions in this metabolic pathway cause porphyrins and their precursors to build up to toxic levels throughout the body — often in the kidneys and skin, although not limited to those organs — while limiting the amount of oxygen carried in the blood.

Although each type of porphyria stems from the loss of a specific enzyme in that pathway, all can be diagnosed by a genetic test, or by examining the levels of porphyrins found in an individual’s blood, urine, or stool.

Genetic tests

Mutations in the genes coding for the different enzymes needed for heme production underlie each type of porphyria. Testing for these mutations, therefore, provides a highly sensitive way to simultaneously screen for and identify a particular type of porphyria.

Urine tests

Urine samples can be collected multiple times over a 24-hour period, or on a single occasion at any given point during the day. The 24-hour urine sample is usually used to monitor the natural variation in urine porphyrin levels throughout the day. A single random sample, however, often suffices. A healthcare provider will be able to determine which of these samples is the best option and provide instructions accordingly.

Such urine testing for porphyria often looks for high levels of the porphyrin precursors porphobilinogen (PBG) and aminolevulinic acid (ALA). Normally colorless, large amounts of PBG in urine convert spontaneously to uroporphyrin, which gives urine a reddish color, and to other molecules that impart it with a brown color. PBG levels are often highest during acute porphyria attacks.

Although PBG is sometimes tested for on its own as a “first-line” porphyria test, it is often measured alongside ALA levels, as the two can indicate different types of porphyria. In ALAD porphyria, for instance, ALA tends to increase while PBG levels may not.

Urine also can be sampled for total porphyrins. Porphyrins can remain in urine much longer than PBG and ALA during acute attacks, such as those caused by hereditary coproporphyria (HCP) and variegate porphyria (VP). However, other medical conditions also can cause urinary porphyrins to increase, making this test alone less specific for porphyria than testing for PBG and ALA.

Blood tests

Measuring total porphyrin levels in the blood is an effective way to screen for cutaneous porphyrias, as porphyrins are rarely found in high quantities there in any other medical condition. A spectrofluorometer, which measures the degree of a liquid’s fluorescence, can be used to detect these porphyrins, which fluoresce a reddish color when exposed to ultraviolet light.

Although the concentration of PBG is typically lower in blood than in urine, a blood test may be needed when urine cannot be collected, as in the case of patients with kidney failure.

An erythrocyte porphyrin test measures the amount of porphyrins in red blood cells, or erythrocytes. This test is used to screen for erythropoietic protoporphyria (EPP) and X-linked protoporphyria, as erythrocytes typically carry more protoporphyrins than any other kind of porphyrins.

Stool tests

Porphyrin levels are unusually high in the feces of patients with HCP and VP, and to a lesser extent, in those with porphyria cutanea tarda (PCT) and EPP. If fecal porphyrin levels are high, physicians may order fractionation tests to separate and identify them, in order to make a more specific diagnosis.

Fractionated porphyrins

Specific types of porphyria can be diagnosed by separating — fractionating — different porphyrins and measuring the quantity of each type present. This procedure can be done on blood, stool, and urine samples, and employs a chemical procedure known as high-performance liquid chromatography, or HPLC. That procedure separates each porphyrin based on its physical and chemical properties.

 

Last updated: April 8, 2021

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