Snapshot A 32-year-old woman presents to the psychiatric emergency room for uncooperative behavior and hysteria. She complains of abdominal pain. While being evaluated, she had a generalized tonic-tonic seizure. She has no family or personal history of seizures. Her serum studies ruled out any metabolic abnormalities that may cause seizures. Neurologic exam showed extensive peripheral neuropathy. Urine showed high titers of porphobilinogen. Introduction Clinical definition acute intermittent porphyria (AIP) is an inherited metabolic disease resulting from deficiency in the heme synthesis pathway porphobilinogen deaminase (PBD) Epidemiology Incidence AIP is the most common type of acute porphyria but still relatively rare 0.13 per year per million persons Demographics women > men 20-40 years of age Risk factors female gender ETIOLOGY Pathophysiology pathobiology deficiency of porphobilinogen deaminase (step 3 in heme pathway, see illustration) attacks are precipitated by an exposure exposure increases demand of the heme pathway resulting in an accumulation of intermediates, aminolevulinic acid (ALA) and porphobilinogen (PBG) which are both neurotoxic precipitating factors most commonly 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 (aka PBGD), encoding PBD 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 vomiting constipation Physical exam vitals tachycardia hypertension neurologic signs in severe attacks loss of tendon reflexes motor stiffness/paralysis the rest of physical exam is often normal Imaging Radiographs abdominal radiography indication often initially obtained due to nonspecific nature of symptoms findings normal Studies Labs serum studies may see hyponatremia urine studies ↑ PBG, aminolevulinic acid, and uroporphyrin III stool studies no fecal porphyrin note, fecal porphyrin may be elevated in other types of porphyrias Differential Small bowel obstruction tenderness on palpation Lead poisoning no elevated PBG in urine Treatment Remove precipitating factors Medical heme infusions indication for severe attacks glucose indications for minor attacks if heme is not available requires close monitoring of serum sodium to exclude hyponatremia Complications Chronic neuropathic pain treatment gabapentin Prognosis Most patients fully recover < 5% have recurrence