P071: Two de novo intronic mutations of GLS gene leading to glutaminase deficiency/autosomal recessive developmental and epileptic encephalopathy 71 (AR-DEE71)

wide range of clinical manifestations even among family members.Advances in genetic testing have enabled earlier diagnosis, leading to more prompt and effective management, even though a cure has not yet been found.Case Presentation: We present a 36-year-old female with a complex medical history marked by progressive neurological symptoms.At 17 years old, the patient developed ataxia and peripheral neuropathy, which gradually worsened.At 23 years old, she began experiencing intractable epilepsy that persisted despite multiple antiepileptic medications, accompanied by episodes of urinary incontinence and a noticeable decline in cognitive function.Over the years, she also experienced recurrent psychotic episodes, further complicating her clinical presentation.Serial neuroimaging revealed white matter hyperintensities in the left frontal lobe, right parietal region, and posterior cingulate gyrus.Initially misdiagnosed with multiple sclerosis, the patient's refractory epilepsy and the unexplained neurologic progression prompted genetic consultation at 36 years of age.Diagnostic Workup: The patient's history and clinical presentation included several indicators suggesting the need for a mitochondrial workup, including multisystem involvement, refractory epilepsy, and intermittent lactic acidosis.Plasma amino acid, urine organic acid, plasma acyl carnitine, and carnitine profile were non-diagnostic.GDF-15 level came back significantly elevated 5155 pg/mL (normal <=750).Combined Mito genome plus Mito focused nuclear gene panel identified two pathogenic variants in POLG.First variant c.2243 G>C (PM3), and second variant c.1399 G>A (PM3).This result is consistent with an autosomal recessive POLG-related disorder if these variants are on opposite alleles (in trans), but parental testing was not possible.