What is the best course of action for an underweight patient presenting with headache, abdominal pain, urinary retention, and decreased appetite, who may be at risk for nutritional deficiencies or metabolic disorders, and possibly acute intermittent porphyria?

Diagnostic Workup for Suspected Acute Intermittent Porphyria

Immediately obtain urinary porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) levels normalized to creatinine on a random spot urine sample—this is the essential first-line test that will confirm or exclude acute intermittent porphyria as the cause of this patient's symptoms. 1, 2

Critical First-Line Testing

Urinary PBG is the most specific and essential diagnostic marker. If significantly elevated (>10 times the upper limit of normal, or >10 μmol/mmol creatinine by mass spectrometry), it confirms an acute porphyria attack. 2 During acute attacks, both ALA and PBG are elevated at least 5-fold above normal. 1

Normal urinary or plasma PBG during acute symptoms definitively excludes AIP as the cause (assuming proper sample handling), allowing you to pursue other diagnoses. 1, 2

Sample Collection Requirements

• Protect all samples from light by covering tubes in aluminum foil to prevent falsely low results 1, 2
• Use a morning spot urine sample, not a 24-hour collection 1, 2
• Refrigerate or freeze samples promptly, as PBG decreases within 24 hours at room temperature 1, 2
• Interpret cautiously if urinary creatinine is below 2 mmol/L, as this can cause falsely elevated results 1, 2

Essential Baseline Blood Work

Once AIP is biochemically confirmed, obtain the following baseline studies:

• Complete blood count (CBC) and ferritin levels to assess for iron deficiency, which is common in young women with AIP and causes chronic symptoms 2, 3
• Comprehensive metabolic panel including electrolytes, as hyponatremia occurs in 25-60% of symptomatic cases during attacks 2, 3, 4
• Estimated glomerular filtration rate (eGFR) at baseline, as AIP poses risk for chronic tubulointerstitial nephropathy 2, 3
• Liver function tests (aminotransferases), as they are elevated in approximately 13% of patients during acute attacks 2, 3, 5

Critical Diagnostic Pitfalls to Avoid

Do not order urinary total porphyrins as a first-line test—it is unhelpful and misleading for diagnosing acute porphyrias. 1, 2 Mild and nondiagnostic elevations in urinary porphyrins (secondary porphyrinurias) are often incorrectly interpreted as indicating AHP and lead to erroneous overdiagnosis. 1

Do not proceed directly to genetic testing without biochemical confirmation. The autosomal dominant acute porphyrias have very low penetrance (approximately 1% for AIP). 1 If patients with non-specific symptoms like abdominal pain were investigated directly with genetic testing, pathogenic variants would be discovered in individuals where symptoms are not caused by the variant, leading to incorrect treatment with potentially serious consequences. 1

Confirmatory Testing After Biochemical Diagnosis

Once biochemical diagnosis is established with elevated PBG/ALA, genetic testing (HMBS gene sequencing) is required to confirm AIP and enable family screening. 2 This should only be performed after demonstrating markedly increased urine PBG/ALA during symptomatic periods. 1

Addressing the Decreased Appetite

The decreased appetite in this patient is likely multifactorial:

• Decreased caloric intake itself can precipitate acute porphyric attacks, creating a vicious cycle 6, 7, 8
• Nausea and vomiting are common autonomic symptoms during acute attacks 1
• Severe abdominal pain naturally suppresses appetite 1

If AIP is confirmed, immediately initiate oral or intravenous dextrose (glucose) to suppress hepatic heme synthesis, which addresses both the underlying pathophysiology and provides needed calories. 3, 6 This is a critical early intervention even before hemin therapy is available. 3

Clinical Context Interpretation

The constellation of headache, abdominal pain, urinary retention, decreased appetite, and underweight status in this patient strongly suggests acute intermittent porphyria. 1 The urinary retention represents autonomic neuropathy, a hallmark of acute attacks. 6, 4 The key diagnostic features indicating possible acute porphyria include intensive abdominal pain without peritoneal signs, acute peripheral neuropathy, and potential encephalopathy. 6

Be aware that mass spectrometry methods have lower detection limits and correspondingly lower upper limits of normal compared to traditional ion-exchange methods, so interpretation must account for the methodology used. 1, 2