Which blood tests should be ordered to confirm suspected porphyria in a patient presenting with unexplained abdominal pain, neuropsychiatric symptoms, or photosensitivity?

Blood Tests to Confirm Porphyria

For suspected acute porphyria with neurovisceral symptoms (abdominal pain, neuropsychiatric features), order urinary porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) normalized to creatinine on a random spot urine sample—if PBG is significantly elevated (>5-10 times upper limit of normal), acute porphyria is confirmed. 1

First-Line Testing for Acute Porphyria (Abdominal Pain, Neuropsychiatric Symptoms)

Essential Tests

• Urinary PBG and ALA with creatinine on a random morning or spot urine sample (NOT 24-hour collection) 1

  • PBG is the most specific marker—if significantly elevated (typically >10 μmol/mmol creatinine), acute porphyria is confirmed 1, 2
  • During acute attacks, both ALA and PBG are elevated at least 5-fold above upper limit of normal 1, 2
  • Normal PBG and ALA during acute symptoms rules out acute porphyria (AIP, VP, HCP, ALAD deficiency) when proper sample handling is followed 1

• Plasma ALA and PBG can be used as alternatives when urine collection is problematic 2

Critical Sample Handling

• Protect all samples from light by covering tubes in aluminum foil—porphyrins degrade with light exposure, causing falsely low results 1
• Refrigerate or freeze samples promptly—PBG decreases within 24 hours at room temperature 1, 2
• Interpret cautiously if urinary creatinine <2 mmol/L, as this causes falsely elevated results 1, 3

Important Pitfalls

• Do NOT order urinary total porphyrins as first-line test—it is unhelpful and misleading for acute porphyria diagnosis 1, 2
• ALA is less specific than PBG and can be elevated in lead poisoning and hereditary tyrosinemia 1
• Mass spectrometry methods have lower reference limits than traditional ion-exchange methods—be aware of which method your lab uses 1, 2

First-Line Testing for Cutaneous Porphyria (Photosensitivity, Bullous Skin Lesions)

Essential Tests

• Plasma porphyrin fluorescence emission spectroscopy on EDTA blood sample 4, 3

  • Fluorescence emission peak wavelength differentiates porphyria types (628-636 nm for EPP/XLEPP) 4
  • Positive in 99% of VP patients, 68% of AIP, 29% of HCP 5

• Random urine sample for total urinary porphyrins (TUP) with fractionation 4, 3

  • PCT shows elevated uro- and heptacarboxyl porphyrins 4
  • Protect from light 3

• Whole blood for erythrocyte porphyrin analysis is essential to identify erythropoietic protoporphyria (EPP) 3

  • Erythrocyte zinc-chelated protoporphyrin elevated in HEP 4

Secondary Tests (Only if First-Line Positive or Symptoms Persist)

• Fecal porphyrin analysis for differentiation between VP, HCP, and PCT 4, 3, 5
  • Coproporphyrin isomer ratio has high specificity for differentiating acute porphyrias 5

Baseline Blood Work for Confirmed Porphyria Patients

Once diagnosis is established biochemically, obtain:

• Complete blood count (CBC) and ferritin—iron deficiency is common in young women with porphyria and causes chronic symptoms 2
• Comprehensive metabolic panel—hyponatremia occurs in 25-60% of symptomatic acute porphyria cases 2
• Estimated glomerular filtration rate (eGFR)—AIP poses risk for chronic tubulointerstitial nephropathy 2
• Liver function tests (aminotransferases)—elevated in ~13% during acute attacks 2

Timing Considerations

• During acute attack: ALA and PBG remain elevated for days after symptoms, unless hemin treatment has been given 1, 2
• Between attacks: In AIP, PBG can remain elevated for months to years after acute episodes 1, 4, 2
• In HCP and VP: ALA and PBG levels can fall quickly after acute attacks 1, 4
• In remission: 15-44% of sporadic AIP patients may have normal urine ALA and PBG when asymptomatic 1

Confirmatory Testing

After biochemical diagnosis is established:

• Genetic testing (HMBS gene for AIP, CPOX for HCP, PPOX for VP) to confirm diagnosis and enable family screening 2, 5
• Mutation detection sensitivity: AIP 98.1%, HCP 96.9%, VP 100% 5
• Do not use genetic testing as first-line—biochemical testing must come first 2