What is the role of the Watson-Schwartz test in diagnosing acute intermittent porphyria (AIP)?

Role of Watson-Schwartz Test in Diagnosing Acute Intermittent Porphyria

The Watson-Schwartz test is a historical qualitative screening test for porphobilinogen (PBG) in urine that has largely been replaced by more sensitive and specific quantitative tests, and should not be used as the primary diagnostic tool for acute intermittent porphyria (AIP).

Diagnostic Approach for AIP

Initial Biochemical Testing

• The diagnosis of AIP requires biochemical testing measuring urinary levels of:

  • δ-aminolevulinic acid (ALA)
  • Porphobilinogen (PBG)
  • Creatinine (for normalization)
  • Porphyrins 1

• A random urine sample is sufficient; 24-hour collection is not necessary 1, 2

• During acute attacks, both ALA and PBG are elevated at least 5-fold above the upper limit of normal 1, 2

Limitations of Watson-Schwartz Test

• The Watson-Schwartz test is a rapid qualitative screening test for PBG that has been available since the 1950s 1
• Despite its historical use, clinical application has been limited due to:
  • Low specificity and sensitivity 2
  • Lack of routine use by most hospitals 1
  • Only becomes positive at PBG concentrations greater than 9 mg/liter 3
  • Requires confirmation with quantitative testing 3

Current Recommended Testing Approach

1. First-line testing: Quantitative measurement of ALA and PBG in a random urine sample normalized to creatinine 1, 2
2. Timing: Testing is most useful during an acute attack 1
3. Confirmation: Genetic testing of the HMBS gene after positive biochemical testing 1, 2

Clinical Considerations

Interpretation of Results

• PBG levels can remain elevated for months to years after an acute attack in AIP 1, 2
• In asymptomatic periods, 15-44% of AIP patients may have normal urine ALA and PBG values 1
• In patients with recurrent attacks (≥4/year), ALA and PBG are typically elevated even between attacks 1, 2
• Normal PBG levels likely rule out AHP as the cause of symptoms 1, 2

Common Diagnostic Pitfalls

• Relying solely on urine porphyrin tests (without ALA and PBG) can lead to misdiagnosis 1
• Secondary porphyrinurias (mild elevations in urinary porphyrins) are more common than actual porphyrias and can lead to overdiagnosis 1
• Nonspecific symptoms of AIP often lead to misdiagnosis and inappropriate treatments 4

Modern Alternatives

• Quantitative ALA and PBG measurements have high sensitivity and specificity 1
• A new rapid test for PBG has been approved in the US (Teco Diagnostics) 1
• Plasma PBG measurement may provide more accurate monitoring of acute attacks than urinary measurements 5

Conclusion

While the Watson-Schwartz test has historical significance in screening for AIP, current guidelines recommend quantitative measurement of urinary ALA and PBG normalized to creatinine as the initial diagnostic test, followed by genetic confirmation. The Watson-Schwartz test should not be relied upon as a primary diagnostic tool due to its limited sensitivity and specificity.