Diagnosis and Management of Acute Hepatic Porphyria

Critical Testing and Diagnosis

The American Gastroenterological Association recommends that a negative urine porphyrin test does not rule out acute hepatic porphyria (AHP), and proper biochemical testing with urinary ALA and PBG levels is necessary to definitively exclude or confirm this diagnosis 1, 2
The European Association for the Study of the Liver discourages urine porphyrin testing alone for diagnosing acute porphyrias, as it leads to false negatives and false positives, and instead recommends testing urinary ALA and PBG measured together with creatinine in a random urine sample 2, 3, 4
The correct first-line test for diagnosing or excluding AHP during an acute attack is urinary ALA and PBG measured together with creatinine in a random urine sample, with a strength of evidence level of high 1, 2

The American Gastroenterological Association recommends measuring urinary ALA, PBG, and creatinine on a random urine sample, preferably morning spot urine, to diagnose AHP 1, 2
The European Association for the Study of the Liver recommends protecting the sample from light by wrapping the collection tube in aluminum foil, as porphyrins are photosensitive, and results should be normalized to creatinine excretion 2, 3, 4
During acute attacks, both ALA and PBG are elevated at least 5-fold above the upper limit of normal, with a strength of evidence level of moderate 1, 5

If PBG is significantly elevated (>5-10x upper limit of normal), acute porphyria is confirmed, with a strength of evidence level of high 1, 5
If both ALA and PBG are normal during symptoms, AHP is effectively ruled out, with the rare exception of ALAD deficiency porphyria, where only ALA is elevated, and a strength of evidence level of moderate 2, 5, 6

Once biochemical testing confirms AHP, genetic testing should identify the specific type by sequencing ALAD, HMBS, CPOX, and PPOX genes, with a strength of evidence level of high 1
First-degree family members require genetic screening once the pathogenic variant is identified, with a strength of evidence level of moderate 1

The American Gastroenterological Association recommends not relying on the Watson-Schwartz or Hoesch qualitative tests alone, and instead using quantitative ALA and PBG measurements, with a strength of evidence level of high 1
The European Association for the Study of the Liver recommends not collecting 24-hour urine samples, and instead using random spot urine, which is sufficient and preferred, with a strength of evidence level of moderate 2, 3