What is the diagnostic workup for Acute Intermittent Porphyria (AIP)?

From the Guidelines

The diagnostic workup for Acute Intermittent Porphyria (AIP) should begin with biochemical testing measuring ALA, PBG, porphyrins, and creatinine in a random urine sample, as this is the most sensitive and specific method for diagnosis, especially during an acute attack 1. The initial diagnosis of AIP should be made by biochemical testing, which measures the levels of certain porphyrin precursors in the urine or plasma.

• The hallmark of acute attacks is significantly elevated ALA and PBG in the urine or plasma, with levels at least 5-fold the upper limit of normal 1.
• A random urine sample is sufficient for diagnosis, and a 24-hour urine collection is not recommended, as the levels of ALA and PBG are high enough to be detected in a random sample 1.
• To adjust for differences in the degree of urinary concentration, ALA and PBG excretion should be normalized to that of creatinine 1.
• Urine porphyrins should not be used alone as a screening test for AIP, as mild and nondiagnostic elevations in urinary porphyrins can lead to erroneous overdiagnosis 1.
• Genetic testing should be used to confirm the diagnosis of AIP in patients with positive biochemical testing, with sequencing of the 4 genes ALAD, HMBS, CPOX, and PPOX leading to ALAD, AIP, HCP, and VP, respectively 1. The diagnostic workup for AIP requires a comprehensive approach, including biochemical testing, genetic testing, and clinical evaluation, to ensure accurate diagnosis and effective management of the disease.
• The use of rapid, qualitative urine PBG tests, such as the Hoesch or Watson-Schwartz test, can be helpful in diagnosing AIP, especially in patients with acute attacks 1.
• The diagnosis of AIP should be considered in patients with recurring severe abdominal pain not ascribable to other causes, especially women aged 15-50 years 1.
• Patients with AIP should be counseled on the chronic and long-term complications of the disease, including neuropathy, CKD, hypertension, and HCC, and need for long-term monitoring 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.

The diagnostic workup for Acute Intermittent Porphyria (AIP) involves:

• Clinical evaluation: Presence of clinical symptoms suggestive of acute porphyric attack
• Laboratory tests: Quantitative measurement of porphobilinogen (PBG) in urine, as well as δ-aminolevulinic acid (ALA) and total porphyrin determinations 2

From the Research

Diagnostic Workup for Acute Intermittent Porphyria (AIP)

The diagnostic workup for AIP involves several tests to confirm the presence of the disease. The key diagnostic indicators include:

• Presence of intermediary metabolites of haem synthesis, such as amino levulinic acid (ALA) and porphobilinogen (PBG) in urine 3, 4, 5, 6
• Specific enzyme assays, including porphobilinogen deaminase (PBGD) activity in erythrocytes 7
• Urine sun drying test to detect the presence of porphyrin 6
• Genetic testing to confirm the diagnosis of AIP 6

Clinical Presentation and Diagnostic Challenges

AIP patients often present with non-specific symptoms, making diagnosis challenging. Common symptoms include:

• Abdominal pain (90% of cases) 3, 4, 7, 6
• Neuropsychiatric manifestations, such as psychosis and seizures 4, 7, 6
• Hyponatremia and altered mentation 4
• Peripheral polyneuropathy and respiratory failure in severe cases 3

Interpretation of Test Results

The interpretation of test results requires consideration of the biological variation of ALA and PBG in healthy individuals and AIP patients. A 2-fold increase in PBG, independent of the baseline concentration, is likely related to the patient's disease and not caused only by analytical and biological variation 5. A high index of suspicion for AIP is necessary, especially in patients with recurrent abdominal symptoms, intractable hyponatremia, and neurological manifestations 4.