What is the best approach to diagnose porphyria?

Diagnosing Porphyria: A Systematic Approach

The diagnosis of porphyria requires specific biochemical testing of urine, blood, and feces, with samples protected from light to avoid false negative results. 1

Initial Diagnostic Approach

First-Line Testing Based on Presentation

1. For suspected acute neurovisceral symptoms:

   • Collect a random urine sample during symptoms for quantitative porphobilinogen (PBG) and δ-aminolevulinic acid (ALA) measurement 1
   • Protect sample from light (cover tube with aluminum foil) 1
   • Ensure urinary creatinine is >2 mmol/L for accurate interpretation 1, 2
   • Results should be available within 24 hours 2

2. For suspected cutaneous porphyria:

   • EDTA blood sample for plasma porphyrin fluorescence emission spectroscopy 2
   • Random urine sample for total urinary porphyrins 2
   • Whole blood sample (essential for diagnosing protoporphyria) 2

Sample Collection Requirements

• Urine samples:

  • Morning or spot urine preferred over 24-hour collections 1
  • Normalize results to creatinine excretion 1
  • PBG is unstable at room temperature (decreases within 24 hours) 1

• All samples:

  • Must be protected from light to prevent degradation 1, 2
  • Process promptly, especially for PBG analysis 1

Interpretation of Results

Acute Porphyrias

• Positive diagnosis: Significantly increased urinary PBG confirms acute porphyria during an attack 1
• Normal PBG: Rules out acute porphyria as cause of current symptoms 1
• ALA interpretation: Less specific than PBG; can be elevated in lead poisoning and hereditary tyrosinemia 1

Cutaneous Porphyrias

• Diagnosis requires specific patterns of porphyrin accumulation in plasma, urine, and/or feces 3
• Plasma fluorescence emission spectroscopy is valuable for initial screening 2

Differentiating Between Porphyria Types

After confirming porphyria, additional testing is needed to determine the specific type:

• Acute hepatic porphyrias:

  • AIP, VP, HCP, ALAD-deficiency porphyria 1
  • Distinguished by patterns of porphyrins in urine, plasma, and feces 1

• Cutaneous porphyrias:

  • PCT, EPP, XLEPP, CEP 3, 4
  • Distinguished by specific porphyrin patterns and clinical presentation 1

Common Pitfalls to Avoid

1. Relying on total urinary porphyrins alone: Can be misleading for acute porphyrias 1

2. Inadequate sample handling:

   • Failure to protect samples from light 1, 2
   • Delayed processing of PBG samples 1

3. Misinterpreting results:

   • False positives with colorimetric methods (penicillin, tienam) 1
   • False negatives with methenamine hippurate 1

4. Overlooking secondary causes of elevated porphyrins:

   • Lead poisoning, liver disease, iron deficiency 4

5. Testing during remission:

   • Normal results don't exclude porphyria in remission or latent carriers 1
   • Between attacks, patients with neurocutaneous porphyrias may have normal urinary porphyrins 5

When to Consider Genetic Testing

• Only after biochemical confirmation of porphyria 3
• Important for family screening and genetic counseling 3
• Limited value in symptomatic porphyrias due to low clinical penetrance 1

Referral to Specialists

• Complex cases should be discussed with porphyria specialist laboratories 1, 2
• Confirmed acute porphyria cases require clinical advice from specialized services 2

Treatment Considerations

For confirmed acute porphyria attacks, treatment with hematin (PANHEMATIN) may be indicated, but only after:

• Confirming diagnosis with elevated PBG 6
• Considering an appropriate period of carbohydrate loading (400g glucose/day for 1-2 days) 6

Remember that early diagnosis and treatment are crucial, as attacks may progress to irreversible neuronal damage if left untreated 6.