The diagnosis of porphyria is often difficult to make, in part due to the fact that the symptoms can mimic many other clinical states and the fact that the disease is sufficiently rare that most doctors have very limited personal experience with it. The recollection that some other member of the family, even a distant cousin, had this problem is often the key to the diagnosis. Since the multiple disease syndromes known as porphyria are all due to defective enzyme functions, there are abnormal accumulations of a variety of compounds involved in the metabolic pathway. Some of these are water-soluble and so are freely excreted in the urine, others are found in feces after being metabolized by the liver and excreted into the bile. The classic laboratory finding that is described is the demonstration of red urine, either immediately on being passed or after standing in bright sun light. This is due either to the excretion of preformed porphyrin molecules or possibly by the nonenzymatic condensation of the high concentration of PBG into tetrapyrrole porphyrin molecules.
The laboratory diagnosis still depends initially on tests, which will identify abnormal concentrations of either the precursors of porphyrins or the porphyrins themselves or both. The compounds, which are usually measured, include PBG, ALA, uroporphyrin and coproporphyrin, and they are found in the urine, feces, plasma, and red blood cells. When the diagnosis of an acute porphyria is considered clinically, the initial screening test should be the determination of the concentration of PBG and ALA in a random sample of urine normalized to creatinine, a measure of kidney function. Porphobilinogen production is elevated in the common acute porphyrias, AIP, VP, and HCP. The term used for this is pathognomonic. The screening tests for PBG and ALA are now obsolete and have been replaced by quantitative tests.
The diagnostic test sample for an acute presentation is a random urine samples. The urine should be collected in an opaque container and refrigerated to prevent the breakdown of the compounds. In non-acute situations or when looking for the chronic porphyrias, the diagnostic tests for urinary PBG, ALA and porphyrin excretion are done on 24-hour collections of urine and require specific preservatives. The urine should be collected in an opaque bottle and refrigerated to prevent the breakdown of the compounds. These tests may be difficult for the patient to complete as the urine must be collected and stored under very specific conditions and not all laboratories can do these tests. Although a sick patient will usually cooperate with the instructions for collection and storage of a 24-hour urine sample, many asymptomatic possible carriers of the gene who are being screened will not bother. In such cases, a random urine samples should be obtained as it can still provide much information.
It is essential that before arranging for these tests, the requesting doctor consult with the laboratory to ensure that the tests are available and also know the recommended procedures as to how and when to collect the blood, stool and urine samples. In addition, there is considerable overlap of the laboratory results between the various diseases, which complicates the difficulties of making a specific diagnosis. It can be very difficult to identify the patients with latent disease, particularly youngsters before the age of puberty.
Some specialized university based referral laboratories will make other tests available using more sophisticated techniques. Theses tests can include measuring the activities of the various enzymes, such as hydroxymethybilane synthase (formerly porphobilinogen deaminase), which is deficient in patients with AIP; fraction of the porphyrins by high performance liquid chromatography (HPLC); and sequencing of the DNA to identify the mutation carried by the patient. The last is particularly important for determining if relatives of a patient are at risk for porphyria or for clarifying difficult cases.
Source: This information originally appeared in a booklet written for the Canadian Porphyria Foundation: A Guide to Porphyria (1991) by Dr. Barry A. Tobe, MD, Ph.D, FRCP(C), Toronto, Ontario, Canada. The content has been updated by Dr. Brian M. Gilfix, MDCM, PhD, FRCPC, DABCC, FACB on 22/03/2015.
Last Updated: 22/March/2015