What is the appropriate diagnostic workup for acute porphyria?

From the Guidelines

The diagnostic workup for acute porphyria should begin with screening tests during an acute attack, including a spot urine test for porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) as recommended by the most recent study 1. A positive PBG test (typically >20 mg/L or >10 mg/g creatinine) during symptoms strongly suggests acute porphyria. This should be followed by quantitative measurements of urinary PBG, ALA, and total porphyrins. If these initial tests are positive, specific testing to determine the type of acute porphyria is necessary, including plasma and fecal porphyrin analysis and erythrocyte enzyme assays. Genetic testing for mutations in specific genes (HMBS for acute intermittent porphyria, CPOX for hereditary coproporphyria, PPOX for variegate porphyria, and ALAD for ALA dehydratase deficiency porphyria) can confirm the diagnosis, as stated in 1. It's essential to collect samples during an acute attack when metabolite levels are highest, as levels may normalize between attacks, and samples should be protected from light and properly preserved, as noted in 1. Additional workup should include basic laboratory tests to rule out other causes of symptoms and assess complications, including:

• Complete blood count
• Comprehensive metabolic panel
• Serum sodium, with hyponatremia being common during acute attacks, as mentioned in 1 MRI of the brain and spine may be indicated if neurological symptoms are present. The diagnostic process requires specialized laboratory expertise, so consultation with a porphyria specialist and referral of samples to a specialized porphyria laboratory is recommended for accurate diagnosis, as emphasized in 1. Key points to consider in the diagnostic workup include:
• Clinical features alone are not specific enough to establish a porphyria diagnosis, as stated in 1
• Diagnosis in a symptomatic patient depends on demonstration of typical patterns of haem precursors, for most diagnoses in urine, faeces, and blood, as noted in 1
• Secondary abnormalities of porphyrin accumulation and excretion are more frequently occurring than the porphyrias, as mentioned in 1
• Genomic testing should not be used for diagnostic screening in a symptomatic patient without prior biochemical testing having demonstrated increased porphyria-related diagnostic markers, as recommended in 1

From the FDA Drug Label

• Before PANHEMATIN therapy is begun, the presence of acute porphyria must be diagnosed using the following criteria:

1. Presence of clinical symptoms suggestive of acute porphyric attack.
2. Quantitative measurement of porphobilinogen (PBG) in urine The single-void urine sample should be refrigerated or frozen without additives and shielded from light for subsequent quantitative δ-aminolevulinic acid (ALA), PBG, and total porphyrin determinations. (Note: the classical Watson-Schwartz or Hoesch tests are considered to be less reliable).

The appropriate diagnostic workup for acute porphyria includes:

• Clinical evaluation: presence of clinical symptoms suggestive of acute porphyric attack
• Quantitative measurement of porphobilinogen (PBG) in urine: using a single-void urine sample that is refrigerated or frozen without additives and shielded from light
• Quantitative δ-aminolevulinic acid (ALA) and total porphyrin determinations: on the same urine sample 2

From the Research

Diagnostic Workup for Acute Porphyria

The diagnostic workup for acute porphyria involves several steps, including:

• Clinical evaluation to identify symptoms such as abdominal pain, autonomic dysfunction, hyponatremia, muscle weakness, or mental symptoms 3
• Laboratory tests to measure porphyrin precursors, such as porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) in urine 4, 5, 6
• Measurement of urine porphobilinogen excretion, which should be more than fivefold elevated to indicate an acute attack 3
• Analysis of urine, plasma, and fecal porphyrins to identify individual acute porphyrias 4
• Mutation screening and identification of the type of acute porphyria, which can be done at the quiescent phase of the disease 3

Laboratory Tests

Laboratory tests for acute porphyria include:

• Porphobilinogen (PBG) quantitation in a random urine sample collected during symptoms 4
• Urine porphyrin excretion (TUP) measurement on the same urine sample 4
• Measurement of delta-aminolevulinic acid (ALA) in urine, which is elevated in patients with acute porphyria 5, 6
• Plasma porphyrin fluorescence emission spectroscopy and random urine sample for TUP to investigate cutaneous porphyria 4

Interpretation of Test Results

Interpretation of test results should consider the biological variation of urinary delta-aminolevulinic acid and porphobilinogen in healthy individuals and patients with acute intermittent porphyria 7

• A 2-fold increase in PBG, independent of the baseline concentration, will be detected with a probability >80% and is most likely related to the patient's disease 7
• The probability of detecting a 100% real change in PBG was 97% in the short-term setting and 80% in the long-term setting 7