Is a urine porphobilinogen (PBG) level at the upper limit of normal concerning in a patient with ongoing pain and a history of potential porphyria attacks?

Urine PBG Level at Upper Limit of Normal in Suspected Porphyria

A urine porphobilinogen (PBG) level of 1.5 (at the upper limit of normal) collected days after an attack but during ongoing pain is not consistent with an acute hepatic porphyria (AHP) attack and suggests an alternative diagnosis should be pursued for the patient's symptoms.

Diagnostic Criteria for Acute Hepatic Porphyria

• During an acute porphyria attack, PBG levels are significantly elevated, typically at least 5-fold above the upper limit of normal 1
• According to recent expert consensus, PBG/creatinine ratio is typically increased to more than 10 times the upper limit of normal during an active attack 1
• A normal PBG level in a symptomatic patient effectively rules out acute porphyria as the cause of symptoms (with the rare exception of ALAD deficiency porphyria) 1

Interpretation of the Patient's PBG Level

• The patient's PBG level of 1.5, which is at the upper limit of normal, does not meet diagnostic criteria for an acute porphyria attack 1
• Even though the sample was collected days after the attack, PBG levels typically remain elevated for weeks to months after an acute attack, particularly in AIP 1
• Studies have shown that PBG can remain elevated in urine for months to years after an acute attack in patients with AIP, with a urinary half-life of approximately 10.6 years 2

Clinical Implications

• The normal PBG level during ongoing pain strongly suggests that the patient's symptoms are not due to acute porphyria 1
• Alternative diagnoses should be considered for the patient's pain symptoms 1
• If clinical suspicion for porphyria remains high despite this result, additional testing could include:
  • Measurement of ALA (δ-aminolevulinic acid) and total urine porphyrins 1
  • Repeat testing during a more acute phase of symptoms 1
  • Genetic testing if there is a strong family history or other compelling reason to suspect porphyria 1

Common Pitfalls in Porphyria Diagnosis

• Mild or non-diagnostic elevations in urinary porphyrins (secondary porphyrinurias) are often incorrectly interpreted as indicating AHP, leading to erroneous overdiagnosis 1
• Urine porphyrins alone should not be used as a screening test for AHP 1
• In patients with frequent symptoms suggestive of acute attacks, normal ALA and PBG levels likely rule out AHP as the etiology of the symptoms 1
• The only exception to this rule is the extremely rare autosomal recessive ALAD deficiency porphyria, where PBG is typically normal but ALA is significantly increased 1

Conclusion for Clinical Decision Making

• Based on current guidelines, a PBG level at the upper limit of normal during ongoing symptoms is not consistent with an acute porphyria attack 1
• The patient's symptoms are most likely due to another cause and further investigation for alternative diagnoses is warranted 1
• If clinical suspicion for porphyria remains, consider measuring both ALA and PBG during a more severe symptomatic episode 1