Watson-Schwartz Test in Diagnosing Acute Intermittent Porphyria
The Watson-Schwartz test is a qualitative rapid screening test for detecting porphobilinogen (PBG) in urine that has historically been used for preliminary diagnosis of acute intermittent porphyria (AIP), but it has been largely replaced by more sensitive and specific quantitative tests measuring urinary ALA and PBG levels. 1, 2
Purpose of the Watson-Schwartz Test
- Provides rapid, qualitative detection of elevated urinary PBG, which is the hallmark biochemical abnormality in AIP
- Serves as a point-of-care screening test when AIP is suspected in patients with compatible symptoms
- Can potentially expedite diagnosis while waiting for more definitive quantitative testing results
Interpretation of Results
- Positive test: Indicates elevated urinary PBG levels, suggesting possible AIP
- Negative test: Generally rules out an acute attack of AIP if performed during symptomatic periods
Limitations of the Watson-Schwartz Test
- Low specificity and sensitivity compared to quantitative tests 2
- Clinical use has been limited due to lack of adoption by most hospitals 1
- Cannot differentiate between different types of acute hepatic porphyrias
- May yield false-negative results, particularly in:
- Asymptomatic periods between attacks
- Patients with HCP or VP where PBG levels may fall quickly after an attack 1
Current Diagnostic Approach for AIP
Initial biochemical testing should measure ALA, PBG, porphyrins, and creatinine in a random urine sample 1, 2
- During acute attacks, both ALA and PBG are elevated at least 5-fold above the upper limit of normal
- The PBG to ALA ratio is approximately 2:1 in patients with normal renal function 2
Confirmatory testing via genetic analysis of the HMBS gene after positive biochemical testing 1, 2
Clinical Pearls and Pitfalls
- AIP diagnosis is frequently delayed, with an average of 15 years from symptom onset to diagnosis in the US and Europe 1
- AIP should be considered in any patient, especially women of childbearing age, with unexplained recurrent, severe abdominal pain 1
- Relying solely on urine porphyrin tests without measuring ALA and PBG can lead to misdiagnosis 1, 2
- Secondary porphyrinurias (mild elevations in urinary porphyrins) are more common than actual porphyrias and can lead to overdiagnosis 2
- PBG levels can remain elevated for months to years after an acute attack in AIP patients 1
- In asymptomatic periods, 15-44% of AIP patients may have normal urine ALA and PBG values 1, 2
Modern Alternatives
- Quantitative measurements of urinary ALA and PBG have high sensitivity and specificity but require specialized laboratories and results may take 1-2 weeks 1
- A newer rapid test for PBG has been approved in the US (Teco Diagnostics) 1
- Genetic testing of the HMBS gene is recommended for confirmation after positive biochemical testing 2
The Watson-Schwartz test can be valuable in resource-limited settings or when rapid screening is needed, but definitive diagnosis requires quantitative biochemical testing followed by genetic confirmation to prevent misdiagnosis and ensure appropriate management of this potentially life-threatening condition.