Case Presentation: A 26-year-old male, recently diagnosed with Acute Intermittent Porphyria (AIP), presented with 3 days of sudden onset severe periumbilical pain exacerbated by eating. He reported 20 episodes of non-bloody emesis accompanied by bilateral facial numbness and right-sided chest pain in the 3 days prior to admission, as well as subjective fever, chills, and diarrhea. Patient sustained 8 similar episodes in the prior 18 months with associated weight loss. Patient reported facial paresthesia with an otherwise unremarkable neurological exam. Laboratories at admission showed hypokalemia and elevated creatinine. Total bilirubin was 2.6 with a normal liver echotexture in ultrasound. Urine porphobilinogen and aminolevulinic acid labs were elevated (206 and 192 respectively) and consistent with an AIP attack. Patient received an extended course of 6 doses of hemin due to persistent symptoms and was discharged with an off-label prescription of givosiran to help prevent future attacks.
Discussion: Acute Intermittent Porphyria (AIP) is a rare autosomal dominant disorder characterized by a deficiency of porphobilinogen-deaminase, an enzyme in heme synthesis. Attacks occur due to upregulation of the enzyme ALA synthase, and are characterized by episodes of abdominal pain, peripheral neuropathies, and constipation. During attacks, hepatic heme is depleted, resulting in induction of delta-aminolevulinic acid synthase (ALAS1). This leads to an accumulation of delta-aminolevulinic acid (ALA) and porphobilinogen (PBG); an elevation of both in urine is the only diagnostic test for API. Hence, AIP can only be diagnosed during an attack. Furthermore, this disease is more common in people of Swedish descent and biologic females, with only 3-8% of AIP patients experiencing recurrent attacks (>3 attacks/year). Our patient is a male of Italian and French descent who experienced an average of 8 attacks a year before diagnosis. The recommended treatment is 4 doses of IV hemin, which downregulates ALAS1 transcription and decreases levels of ALA/PBG. While awaiting hemin infusion, carbohydrate loading via dextrose should be started to assist with downregulation of ALAS1 transcription. More recently, givosiran, an RNA interference therapy that inhibits ALAS1 expression and is FDA approved for Acute Hepatic Porphyria, has been successfully used in the treatment of AIP.
Conclusions: Due to its vague presentation and diagnostic logistical challenges, a diagnosis of AIP is commonly elusive, and many patients are frequently misdiagnosed in emergency departments. A careful neurological exam revealing peripheral neuropathy can lead a clinician to consider AIP. This case reinforces the significance of conducting a thorough history and examination, as well as considering a broad differential diagnosis, particularly in young patients presenting with severe abdominal pain and unremarkable complementary testing. A high index of suspicion is key to diagnosing AIP as testing will only be diagnostic during an attack