What blood work is necessary for the diagnosis of acute intermittent porphyria (AIP)?

Blood Work for Acute Intermittent Porphyria

The essential blood work for diagnosing acute intermittent porphyria is plasma ALA and PBG measurement, though urinary ALA and PBG (normalized to creatinine) remain the gold standard first-line tests during acute symptoms. 1

First-Line Diagnostic Tests

Primary Markers (During Acute Symptoms)

• Urinary porphobilinogen (PBG) is the most specific and essential test—if significantly elevated (typically >10 times upper limit of normal, or >10 μmol/mmol creatinine by mass spectrometry), it confirms an acute porphyria attack 1
• Urinary delta-aminolevulinic acid (ALA) should be measured alongside PBG, though it is less specific than PBG and can be elevated in lead poisoning and hereditary tyrosinemia 1
• Plasma ALA and PBG can be used as alternatives to urine testing and are particularly useful when urine collection is problematic 1
• Normal urinary or plasma PBG during acute symptoms excludes AIP as the cause (assuming proper sample handling) 1

Critical Sample Handling Requirements

• Protect all samples from light by covering tubes in aluminum foil to prevent falsely low results 1
• Use a spot urine sample (morning preferred) rather than 24-hour collection, with results normalized to urine creatinine 1
• Refrigerate or freeze samples promptly, as PBG decreases within 24 hours at room temperature 1
• Interpret results cautiously if urinary creatinine is below 2 mmol/L, as this can cause falsely elevated results 1

Baseline Blood Work for Confirmed AIP Patients

Essential Laboratory Monitoring

• Complete blood count (CBC) and ferritin levels at baseline and at least yearly to assess for iron deficiency, which is common in young women and causes chronic symptoms 1
• Comprehensive metabolic panel including electrolytes, as hyponatremia occurs in 25-60% of symptomatic cases during attacks 1
• Estimated glomerular filtration rate (eGFR) at baseline and regularly thereafter, as AIP poses risk for chronic tubulointerstitial nephropathy 1
• Liver function tests (aminotransferases) at baseline, as they are elevated in ~13% of patients during acute attacks and in some asymptomatic patients 1

Important Diagnostic Pitfalls

What NOT to Order

• Avoid urinary total porphyrins as a first-line test—it is unhelpful and misleading for diagnosing acute porphyrias 1
• Do not rely on screening tests (qualitative PBG tests) due to low specificity and sensitivity; always confirm with quantitative assays 1

Interpretation Caveats

• In known AIP patients during attacks, expect PBG to increase significantly above their baseline, as PBG typically remains elevated for years after acute episodes 1
• Hemin treatment can lower or normalize PBG excretion if sampling occurs during or shortly after treatment 1
• The PBG/ALA ratio is approximately 2:1 in AIP patients with normal renal function, but increases with declining glomerular filtration 1
• Mass spectrometry methods have lower detection limits and correspondingly lower upper limits of normal compared to traditional ion-exchange methods 1

Confirmatory Testing

• Once biochemical diagnosis is established, genetic testing (HMBS gene sequencing) is required to confirm AIP and enable family screening 1
• Genetic testing should not be used as first-line testing due to lack of common mutations (except in Scandinavian populations with founder mutations) 1