Porphobilinogen
Updated: Sep 30, 2020
Author: Roman Bronfenbrener, MD; Chief Editor: Eric B Staros, MD
Porphobilinogen (PBG) is measured in patients with symptoms that suggest acute intermittent porphyria, variegate porphyria, or hereditary coproporphyria.
Porphobilinogens: 0-2 mg/24 hr or 0-8.8 μmol/day (SI units)[1]
Urinary porphobilinogen (PBG) levels are measured in the evaluation of neurovisceral porphyrias, namely acute intermittent porphyria, variegate porphyria, and hereditary coproporphyria.[2]
Acute attacks are associated with drastic elevations in the urinary porphobilinogen level to several multiples of the upper limit of the reference range, generally 50-200 mg/24 hours; elevated porphobilinogen levels in the presence of appropriate clinical symptoms is diagnostic of porphyria.[3, 4]
Rarely, falsely elevated results may be seen in patients with hepatic impairment due to hepatitis, hepatocellular carcinoma, or lead poisoning.[5, 6]
The utility of a porphobilinogen level within the reference range depends on the patient’s current presentation. An acute attack with a porphobilinogen level within the reference range effectively rules out porphyria as a cause of the patient’s symptoms. However, patients with a distant history that suggests porphyria may have porphobilinogen levels within the reference range, particularly if they have had prolonged disease latency. These patients may be evaluated further with enzyme activity measurements or gene analysis.[5]
Urinary porphobilinogen (PBG) is ideally measured during an acute porphyric attack as a random spot test. Twenty-four–hour levels may also be obtained.
The sample should be collected with a urinalysis container or 24-hour urine container.
All specimen containers should be protected from light to prevent porphobilinogen degradation.
If the anticipated time until the test can be delivered to the laboratory and started is less than 4 days, the sample may be refrigerated. Otherwise, freezing allows up to 1 month for the test to be performed.[7]
It is important to note that porphobilinogen is not measured in the urine porphyrins assay; porphobilinogen needs to be measured separately.[8]
Porphobilinogen (PBG) is a pyrrole derivative and an essential component of the heme synthesis pathway. It is formed in the cytoplasm from aminolevulinic acid (ALA) and is then polymerized by the enzyme porphobilinogen deaminase (hydroxymethylbilane synthase) to hydroxymethylbilane. Porphobilinogen is water soluble and is minimally reabsorbed by the kidney; urine levels are therefore the most appropriate diagnostic method.[5]
Under physiologic conditions, porphobilinogen does not accumulate. However, in patients with inherited deficiencies in the enzyme porphobilinogen deaminase, provoking factors such as alcohol use, hormonal effects, or medications drive heme synthesis and overwhelm the limited enzyme capacity. As a result, these individuals can quickly develop dysautonomic symptoms (hypertension and tachycardia), neuropathic and psychiatric illness, and recurrent bouts of severe abdominal pain.[3, 5, 8]
Porphobilinogen is measured in patients with symptoms that suggest acute intermittent porphyria,[9, 10] variegate porphyria, or hereditary coproporphyria. Patients with an elevated porphobilinogen levels can undergo further testing to determine the subtype of porphyria present. During an acute attack, random spot testing is sufficient and shows several fold elevation of porphobilinogen levels above the upper limit of the reference range. In patients with latent disease, a 24-hour urine collection can be performed to increase sensitivity; however, a value within the reference range does not effectively rule out porphyria.