To illustrate a rare atypical presentation of HMBS-related acute intermittent porphyria (AIP) in a patient with abnormal brain lesions and focal seizures who then developed demyelinating neuropathy.

AIP typically involves a triad of severe abdominal pain, neurological symptoms, and autonomic dysfunction. The incidence of symptomatic AIP in the US is estimated to be about 5 per 100,000 people. Seizures can occur in individuals with AIP, with a lifetime prevalence of 5.1% in symptomatic AIP. 

Case report

A 16-year-old African American woman with median arcuate ligament syndrome, hypertension and psychogenic nonepileptic seizures was evaluated for recurrent episodes of abdominal pain and vomiting (thought to be related to cannabinoid hyperemesis syndrome) followed by disinhibited behavior, focal onset seizures, and encephalopathy. Neuroimaging during attacks showed multifocal cortical and subcortical T2/FLAIR hyperintense lesions with patchy enhancement. Serum and spinal fluid analysis for autoimmune and infectious causes were negative. She was initially suspected to have posterior reversible encephalopathy syndrome (PRES) in the setting of uncontrolled hypertension, less likely autoimmune encephalitis or vasculitis. The episodic nature of her neuropsychiatric and abdominal symptoms with resolution of imaging abnormalities after attacks, followed by the development of an unexplained progressive extensor hand weakness, led to metabolic testing that revealed highly elevated urine porphobilinogen and aminolevulinic acid. Genetic testing then confirmed a heterozygous likely pathogenic variant in HMBS, NM_000190.3:c.761T>C;p.(L254P). Nerve conduction studies showed a demyelinating polyneuropathy, which is unusual as AIP is most often associated with axonal neuropathy. 

We present a case of AIP with atypical features in a young African American woman. Given the serious clinical implications and unique treatment of AIP, it should be considered in the evaluation of adolescents with episodic abdominal pain, neuropsychiatric symptoms, and atypical neuroimaging findings, especially when conventional infectious and autoimmune evaluations are unrevealing.