Introduction: FARS2 deficiency is a rare mitochondrial disorder that affects mitochondrial phenylalanyl-tRNA synthetase that transfers phenylalanine to its cognate tRNA in mitochondria. It is primarily associated with early onset epileptic encephalopathy and developmental delay. However, adult-onset presentations are exceedingly rare and frequently overlooked. We describe a rare and a diagnostically challenging presentation of late onset FARS 2 deficiency presenting as super refractory status epilepticus with persistent hyperammonemia. This report expands the known clinical phenotype and highlights the importance of early metabolic evaluation in unexplained status epilepticus. Description: A 25-year-old female with polycystic ovarian syndrome presented with new onset seizures initially treated with levetiracetam and was discharged with neurology follow-up. Within 24 hours, she presented back with super refractory status epilepticus, unresponsive to multiple antiepileptic drugs, requiring intubation for airway protection and high-dose sedation to achieve burst suppression on EEG. Status epilepticus persisted despite therapy requiring over 30 days in a medically induced coma. Her ICU course was further complicated by persistent hyperammonemia with elevated liver enzymes, unresponsive to lactulose, rifaximin and levocarnitine. She was emergently dialyzed because of diffuse cerebral edema noted on CT head. Hyperammonemia associated with elevated liver enzymes raised suspicion for urea cycle disorder. She was started on a low protein diet, which led to significant improvement in her seizure control. Advanced testing identified by biallelic pathogenic variants in the FARS2 gene, confirming FARS2 deficiency- a rare mitochondrial disorder. Patient’s presentation fits well with the late onset epilepsy phenotype without any spasticity. Discussion: This patient presented with elevated and persistent hyperammonemia with cerebral edema and status epilepticus refractory to anti-epileptic medication. This presentation should prompt consideration for rare metabolic disorder such as FARS 2 deficiency. Recognizing this early enables targeted nutritional therapy and prevents prolonged futile escalation of antiepileptic drugs.
Kota et al. (Sun,) studied this question.