A 59 year old man with a history of acute intermittent porphyria was admitted with weakness and subjective chills. Exam revealed severe proximal muscle weakness and areflexia. Blood cultures grew E. coli, treated with ceftriaxone. Laboratory testing was notable for elevated urinary porphyrins, normal creatine kinase of 23 IU/L (normal 47-322), cortisol 30.8 ug/dL (normal 2-20) and TSH 1.8 uIU/mL (normal 0.3-4.2). MRIs of the brain and cervical spine were unremarkable. CSF analysis was normal. EMG revealed an acute generalized motor polyneuropathy, predominantly involving proximal muscles.
His weakness was attributed to porphyric neuropathy in the setting of infection. Despite treatment with four infusions of hemin, he had significant weakness at the time of discharge. He was later readmitted with progressive quadriparesis and respiratory failure requiring intubation; he died two months after his initial admission.
Acute intermittent porphyria (AIP) is the most common subtype of porphyrias, which are a rare group of diseases caused by genetic mutations leading to defective heme synthesis. Prevalence of AIP is estimated at 5 cases per 100,000 people worldwide. AIP is characterized by intermittent attacks triggered by medication use, infection or increased metabolic demand. Presenting symptoms are non-specific and highly variable, including abdominal pain, peripheral neuropathy and autonomic dysfunction. Porphyric neuropathy (PN) is a well-recognized complication that affects between 10 to 40 percent of acute episodes of AIP. PN preferentially affects proximal motor neurons and weakness is typically more severe in the upper extremities. Attacks can range in severity from mild weakness to quadriplegia and can involve the respiratory muscles leading to respiratory failure.
The relative rarity and non-specific symptoms of AIP and PN require a high index of suspicion to make the correct diagnosis. The presentation can mimic acute Guillain-Barre; however diagnosis of PN is supported by elevated urinary porphyrins, EMG with primarily proximal axonal polyneuropathy, and normal CSF analysis without albuminocytologic dissociation. The mainstays of therapy are prompt identification and treatment of acute triggers for attack (i.e. cessation of offending medications, treatment of infection) and intravenous hemin infusions, aimed at inhibiting the activity of ALA synthase to decrease heme biosynthesis in the liver. The efficacy of hemin has not been well established in high-quality trials, but many published case series and reports suggest improved outcomes. Current recommendations support initiating hemin as soon as the diagnosis of an acute attack of porphyria is made.
Porphyric neuropathy is a rare but important cause of progressive flaccid quadriparesis that can mimic the presentation of Guillain-Barre. Patients suspected of having this condition require prompt diagnosis and treatment with intravenous hemin and supportive care.