What lab tests are recommended to screen an adult for porphyrias (a group of disorders that result from a buildup of natural chemicals that produce porphyrin in the body)?

Laboratory Testing for Screening Adults for Porphyrias

The first-line laboratory test for screening adults for porphyrias is urinary porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) measurement in a random urine sample, with samples protected from light. 1

Initial Screening Tests Based on Clinical Presentation

For Acute Neurovisceral Symptoms:

• First-line test: Urinary PBG and ALA measurement

  • Samples must be protected from light (cover collection tubes with aluminum foil)
  • Use a morning or spot urine sample (not 24-hour collection)
  • Results should be normalized to creatinine excretion
  • Samples with urinary creatinine <2 mmol/L should be interpreted with caution 1, 2

• Interpretation:

  • Normal PBG results rule out an acute porphyria attack
  • During an acute attack, PBG is typically elevated >10 times the upper limit of normal
  • PBG is highly specific for acute porphyria attacks 1
  • ALA is less specific than PBG (can be elevated in lead poisoning and hereditary tyrosinemia)

For Cutaneous Symptoms:

• First-line tests:
  • EDTA blood sample for plasma porphyrin fluorescence emission spectroscopy
  • Whole blood for total erythrocyte protoporphyrin
  • Random urine sample for total urinary porphyrins 1, 2

Second-Line Testing for Specific Porphyria Types

Once screening tests are positive, further testing is needed to determine the specific type of porphyria:

1. For acute porphyrias (AIP, VP, HCP):

   • Analysis of urine, plasma, and fecal porphyrin patterns
   • Enzyme activity measurements (e.g., HMBS activity for AIP)
   • Plasma fluorescence emission spectroscopy (particularly for VP)

2. For cutaneous porphyrias (PCT, EPP, CEP):

   • Urine, plasma, and fecal porphyrin patterns
   • Erythrocyte enzyme assays
   • Erythrocyte protoporphyrin levels and zinc/metal-free protoporphyrin ratio 1

Important Pre-analytical Considerations

• Light protection: All samples must be protected from light to avoid falsely low results
• Sample stability: PBG starts to decrease within 24 hours at room temperature
• Urinary creatinine: Must be measured to normalize results; samples with creatinine <2 mmol/L may give falsely elevated results 1
• Timing: For acute attacks, collect samples during symptomatic periods when possible

Common Pitfalls to Avoid

1. Relying on urinary total porphyrins alone: This is unhelpful and potentially misleading as a first-line test for acute porphyrias 1

2. Misinterpreting normal results during remission: Normal PBG/ALA results do not exclude an acute porphyria in remission or a latent porphyria 1

3. Inadequate sample handling: Light exposure can cause falsely low or negative results

4. Using 24-hour urine collections: These are not recommended; morning or spot samples are preferred 1

5. Analytical interferences:

   • Colorimetric PBG methods: false negatives with methenamine hippurate; false positives with tienam and penicillin
   • Dilute urine samples can lead to misleading fluorescence results 1

After biochemical confirmation of porphyria, genetic testing should be performed to identify the specific mutation, which is crucial for family screening and genetic counseling 3.