Case Presentation: A 19-year-old male with history of VACTERL, end-stage kidney disease with kidney transplant 7 years prior, scoliosis with T8-L2 fusion 8 years prior, reversible posterior leukoencephalopathy syndrome (PRES), depression, and recent admission for suspected cannabinoid hyperemesis syndrome presented to the ED after a fall due to weakness, and recurrent nausea and vomiting.Physical exam was notable for diffuse weakness more prominent in proximal muscles with diminished reflexes sparing the ankles. Initial labs were notable for serum creatinine of 5.02 (baseline of 3). He was admitted to a general pediatrics service for evaluation of his new weakness and management of GI symptoms and acute kidney injury. Spine radiographs and brain MRI were unrevealing. CSF protein was slightly elevated but had no pleocytosis. Creatine kinase was within normal limits. Neurology recommended an EMG, which showed a patchy slowing of motor conduction velocities (as can be seen in neuropathy secondary to chronic renal disease), but no findings or evidence suggestive of Guillain-Barre Syndrome, myopathy, or neuromuscular junction disorder. These results with his clinical picture seemed most consistent with a peripheral neuropathic process. He was treated empirically with IVIG with equivocal improvement. Over time team members noted concerns for significant functional overlay of his weakness due to fluctuations in mood and motivation. He had a protracted hospital stay of one year due to worsening weakness, severe malnutrition, and requirement of supportive measures including intermittent intensive care, G-tube placement, hemodialysis, electroconvulsive therapy, and daily physical and occupational therapy. Late in his hospital course, the genetics service was consulted for otherwise unrelated lab abnormalities and suggested whole exome sequencing given lack of a unifying diagnosis. Three months later, this testing resulted with a pathogenic HMBS gene variant associated with acute intermittent porphyria (AIP). Serum and urine porphyrin profile subsequently confirmed the diagnosis. Multiple medications were removed due to association with AIP flares with some improvement of mood and conditioning prior to discharge.

Discussion: AIP is a neurovisceral porphyria caused by a variably penetrant, autosomal dominant gene mutation for the enzyme porphobilinogen deaminase involved in heme biosynthesis. It clinically manifests with acute attacks of neurovisceral symptoms, such as abdominal pain, peripheral neuropathy, dysautonomia, and bladder dysfunction. Other neurological symptoms include seizures and PRES, and it can also present with a variety of neuropsychiatric manifestations.Initial evaluation consists of measurement of porphobilinogen and total porphyrins in the urine, and many also recommend measurement of delta-aminolevulinic acid. However, investigation for AIP is often not explored unless there is a protracted course or multiple presentations because symptoms are non-specific and overlap with other common conditions. In this patient, diagnosis was dramatically delayed because of attribution of manifestations to other medical conditions

Conclusions: AIP is a relatively rare diagnosis with multiple nonspecific neurovisceral symptoms, which can be debilitating and progressive. A high index of suspicion is necessary for diagnosis as early detection can reduce long-term complications.