The SERAC1 gene encodes a protein which is involved in the remodeling of the phospholipid phosphatidylglycerol. Phosphatidylglycerol is found at the interface between mitochondria and endoplasmic reticula, and is essential for proper mitochondrial function and intracellular cholesterol trafficking. Mutations in the SERAC1 gene impair mitochondrial function, and are most commonly associated with MEGDEL and Leigh syndrome. These patients typically present in childhood with developmental delay, spasticity, dystonia, seizures, optic atrophy, and sensorineural hearing loss. Some patients present later in their adolescent years or in early adulthood with parkinsonian symptoms.

 We describe a 25 year-old Hispanic male with a past medical history of retinitis pigmentosa and recurrent episodes of a few days of encephalopathy, fever, and unilateral weakness or parasthesias since the age of 17. He presented to our facility with encephalopathy, fever, and right-sided weakness, and deteriorated to the point of intubation. His hospital course was complicated by respiratory failure eventually requiring tracheostomy, and intractable clinically-evident seizures with no EEG correlate. MRI revealed unilateral left hemispheric edema and gyral enhancement, as well as right temporal encephalomalacia. Infectious, autoimmune, and neoplastic work-up proved unrevealing. Further questioning revealed a history of consanguinity between the parents. A muscle biopsy to evaluate for possible mitochondrial disorder revealed neurogenic atrophy. EMG/NCV revealed a sensorimotor demyelinating polyneuropathy with secondary axonal loss. His whole exome sequencing revealed a homozygous variant of unknown significance in the SERAC1 gene.

Our case illustrates a previously undescribed phenotype of SERAC1 deficiency, with demyelinating sensorimotor polyneuropathy and no basal ganglia involvement. While most patients often present early-on with symptoms such as dystonia, hearing loss, developmental delay, or spasticity, our patient was instead a relatively healthy, functioning young male who presented with recurrent episodes of fever, encephalopathy, and weakness, and had gone previously undiagnosed.