What lab tests can be ordered to diagnose porphyria?

Laboratory Testing for Porphyria

Order a random spot urine sample for porphobilinogen (PBG), delta-aminolevulinic acid (ALA), and creatinine as the key diagnostic test for suspected acute porphyria. 1

First-Line Diagnostic Test

• Spot urine for PBG, ALA, and creatinine is the gold standard screening test when acute porphyria is suspected, particularly in patients with recurrent severe abdominal pain without identifiable cause 1, 2
• PBG is the most specific marker—if significantly elevated (>10 mg/g creatinine or >5-fold upper limit of normal), it confirms acute hepatic porphyria 1, 3
• Normal PBG levels during symptomatic periods effectively exclude acute porphyria as the cause of current symptoms 1, 3
• ALA should be measured alongside PBG but is less specific, as it can be elevated in lead poisoning and hereditary tyrosinemia 1, 3

Critical Sample Collection Requirements

• Protect all samples from light by covering tubes in aluminum foil to prevent falsely low results from porphyrin degradation 1, 3
• Use a morning or random spot urine sample, not a 24-hour collection 1, 3
• Normalize all results to urinary creatinine to account for urine concentration 1, 3
• Process samples promptly, as PBG decreases within 24 hours at room temperature 1, 3
• Interpret results cautiously if urinary creatinine is <2 mmol/L, as this can cause falsely elevated results 1, 3

Important Testing Pitfalls to Avoid

• Do not order urinary total porphyrins as a first-line screening test—this is unhelpful and potentially misleading for diagnosing acute porphyrias 1, 3
• Testing is most informative when performed during symptomatic periods, as levels may normalize during remission 1
• If only ALA is elevated without PBG elevation, check lead levels and urine organic acids to exclude lead poisoning and hereditary tyrosinemia 1

Alternative Testing Options

• Plasma ALA and PBG can be used as alternatives to urine testing when urine collection is problematic 3
• Mass spectrometry methods are increasingly common and have lower detection limits than traditional ion-exchange chromatography methods 1

Additional Testing for Cutaneous Porphyrias

• For suspected cutaneous porphyria (skin photosensitivity), order EDTA blood for plasma porphyrin fluorescence emission spectroscopy and random urine for total porphyrins 4
• Whole blood porphyrin analysis is essential to identify erythropoietic protoporphyria 4
• Fecal porphyrin collection is only needed if first-line tests are positive or clinical symptoms persist 4

Confirmatory and Follow-Up Testing

• Once biochemical diagnosis is established with elevated PBG, proceed to genetic testing (sequencing of HMBS, CPOX, PPOX, or ALAD genes) to determine the specific type of acute hepatic porphyria and enable family screening 1, 3
• For confirmed cases, baseline monitoring should include liver enzymes, creatinine, eGFR, and liver ultrasound 1