What is the initial diagnostic test to order for a suspected case of acute hepatic porphyria in an adult patient presenting with abdominal pain, neurological symptoms, or psychiatric disturbances?

Initial Diagnostic Test for Acute Hepatic Porphyria

Order a random spot urine sample measuring porphobilinogen (PBG), δ-aminolevulinic acid (ALA), porphyrins, and creatinine—this is the key diagnostic test for suspected acute hepatic porphyria. 1

Why This Test First

The American Gastroenterological Association explicitly identifies this as the initial diagnostic test for AHP, and it should be ordered whenever you suspect the diagnosis, particularly in women aged 15-50 years with unexplained recurrent severe abdominal pain. 1

Key Testing Details

• Use a random spot urine sample—a 24-hour urine collection is NOT recommended and unnecessary. 1, 2
• Protect the sample from light by wrapping the collection tube in aluminum foil, as porphyrins are photosensitive. 2
• Morning spot urine is preferred when possible. 2
• Results must be normalized to creatinine to adjust for urinary concentration differences. 1

Interpreting Results

Positive for AHP

• Both ALA and PBG elevated ≥5-fold above upper limit of normal confirms acute hepatic porphyria during an attack. 1, 2
• During acute attacks, the mean PBG excretion can be 50-fold above reference intervals. 3
• If PBG is significantly elevated (>5-10x upper limit of normal), acute porphyria is confirmed. 2

Normal Results

• If both ALA and PBG are normal during symptoms, AHP is effectively ruled out as the cause. 1, 2
• This excludes AHP with high confidence, allowing you to pursue other diagnoses. 2

Special Case: Only ALA Elevated

• If only ALA is elevated without PBG elevation, this suggests ALAD deficiency porphyria (extremely rare, fewer than a dozen cases worldwide). 4
• In this scenario, check lead levels and urine organic acids to rule out lead poisoning and hereditary tyrosinemia, which can mimic this pattern. 1, 4

Critical Pitfalls to Avoid

Do NOT Order Urine Porphyrins Alone

• Urine porphyrins should NOT be used as a screening test for AHP. 1, 2
• The American Gastroenterological Association and European Association for the Study of the Liver both strongly discourage this practice because it leads to false negatives and false positives. 2
• Mild, nondiagnostic elevations in urinary porphyrins (secondary porphyrinurias) are often incorrectly interpreted as indicating AHP, leading to erroneous overdiagnosis. 1
• A negative urine porphyrin test does NOT rule out AHP—proper biochemical testing with urinary ALA and PBG is necessary. 2

Timing Considerations

• Testing is most informative when done while patients are symptomatic. 1
• ALA and PBG can remain elevated for days to months after an acute attack (unless treated with intravenous hemin), so testing shortly after symptoms is still valid. 1
• In patients with sporadic attacks, 15-44% can have normal urine ALA and PBG when asymptomatic, so normal results between attacks don't exclude the diagnosis. 1
• In patients with recurrent attacks, ALA and PBG are typically elevated even at baseline between attacks. 1

Qualitative Tests Are Insufficient

• Do NOT rely on Watson-Schwartz or Hoesch qualitative tests alone—use quantitative ALA and PBG measurements. 2
• While a new rapid PBG test (Teco Diagnostics) was recently approved in the United States, quantitative measurements remain the gold standard. 1

Next Steps After Positive Biochemical Testing

Once biochemical testing confirms AHP with elevated ALA and PBG:

1. Proceed to genetic testing by sequencing the four genes: ALAD, HMBS, CPOX, and PPOX to determine the specific type of AHP (ALAD porphyria, acute intermittent porphyria, hereditary coproporphyria, or variegate porphyria). 1, 2

2. Screen first-degree family members with genetic testing once the familial pathogenic variant is identified. 1, 2

3. Initiate treatment promptly with intravenous hemin if clinically indicated, as early treatment improves outcomes. 1

Clinical Context for Suspicion

Consider ordering this test in:

• Women aged 15-50 years with unexplained recurrent severe abdominal pain without clear etiology after initial workup. 1
• Any patient with recurrent severe abdominal pain, especially if associated with neurological symptoms (neuropathy, muscle weakness), psychiatric disturbances, or autonomic dysfunction (tachycardia, hypertension). 1, 5
• Patients with acute/subacute neuropathy of unclear etiology—it is mandatory to exclude AHP in any acute painful neuropathy. 5