Acute Intermittent Porphyria

Snapshot

• An 28-year-old woman presents with colicky abdominal pain. She fidgets around and sporadically has weeping spells, reports tingling in her fingers and toes, and has no significant past medical history with no official psychiatric history. On physical exam, she is found to be tachycardic. Her abdominal exam is normal, without tenderness on palpation. Neurologic exam is normal. Abdominal radiographs are completely normal. Porphobilinogen was found to be positive in high titers in her urine.

Introduction

• Clinical definition
  • acute intermittent porphyria (AIP) is an inherited metabolic disease resulting from deficiency in the heme synthesis pathway enzyme porphobilinogen deaminase (PBD)
• Epidemiology
  • incidence
    • AIP is the most common type of acute porphyria
      • still relatively rare
  • demographics
    • women > men
    • 20-40 years of age
  • risk factors
    • female gender
• Pathophysiology
  • pathobiology
    • deficiency of PBD, step 3 in heme pathway  
    • attacks are precipitated by an exposure
      • exposure increases demand of the heme pathway
        • this results in accumulation of intermediates aminolevulinic acid (ALA) and porphobilinogen (PBG)
          • both are neurotoxic
      • precipitating factors
        • most common drugs
          • cytochrome P-450 inducers
          • anticonvulsants
          • oral contraceptive pills
        • smoking
        • infection
        • starvation
        • fluctuating hormones (menstrual cycle in women)
• Genetics
  • inheritance pattern
    • autosomal dominant
  • mutations
    • HMBS (also known as PBGD), encoding PBD
• Prognosis
  • most patients fully recover
• < 5% have recurrence

Presentation

• Symptoms
  • often nonspecific and vague
  • primary symptoms (5 P’s) 
    • severe abdominal pain without tenderness on palpation
    • neurological symptoms
      • polyneuropathy
      • seizures, weakness, and paralysis
    • psychiatric symptoms
      • anxiety and insomnia
    • port wine-colored urine
    • precipitated by an exposure
• Physical exam
  • vitals
    • tachycardia
    • hypertension
• the rest of physical exam is often normal

Imaging

• Radiographs  
  • abdominal radiography
    • indications
      • often initially obtained due to nonspecific nature of symptoms
    • findings
• normal

Studies

• Labs
  • serum studies
    • may see hyponatremia
  • urine studies
• ↑ PBG, aminolevulinic acid

Differential

• Small bowel obstruction
  • tenderness on palpation
• Lead poisoning 
• no elevated PBG in urine

Treatment

• Remove precipitating factors
• Medical
  • heme and glucose
    • indications
      • for symptomatic attacks
• to prevent permanent neurologic damage

Complications

• Chronic neuropathic pain
  • treatment
    • gabapentin