A case report of combined oxidative phosphorylation deficiency 35 (COXPD35) in Palestine caused by novel compound heterozygous TRIT1 variants

Rationale: Combined oxidative phosphorylation deficiency 35 (COXPD35) is an extremely rare mitochondrial disorder inherited in an autosomal recessive pattern. It results from pathogenic variants in the TRIT1 gene, leading to hypomodified cytosolic and mitochondrial tRNAs. We report the first identified case of COXPD35 in Palestine, resulting from 2 novel variants of the TRIT1 gene. Patient concerns: A 2-year-and-6-month-old female patient with seizures, neurodevelopmental delay, microcephaly, dysmorphic facial features, abnormal electroencephalogram (EEG), and thinning of the corpus callosum on Brain magnetic resonance imaging, presenting to the Emergency Department with status epilepticus, and right lower lobe pneumonia. Diagnoses: Combined oxidative phosphorylation deficiency 35 (COXPD35) caused by 2 novel TRIT1 variants that have never been previously reported in the literature, diagnosed clinically, and were identified by Whole-exome sequencing (WES) and confirmed by Sanger sequencing. Interventions: The patient received 1 shot of IV diazepam 0.3 mg/kg after IV cannulation, followed by IV ceftriaxone 500 mg twice daily, IV hydrocortisone 20 mg every 4 hours, and albuterol, ipratropium bromide, and hypertonic saline nebulizers regularly. Additionally, she was given intravenous fluids at a rate of 60 mL/h of 5% dextrose saline. She was given a 200 mg dose of phenytoin IV for seizure control. Upon clinical suspicion of a mitochondrial disease, WES was performed, followed by Sanger sequencing for confirmation of the findings. Outcomes: The patient clinically improved, with cessation of seizures, recovery from pneumonia, and confirmed diagnosis of COXPD35. Lessons: The identification of new TRIT1 variants and the expanding phenotypic spectrum of COXPD35 provides insights into its clinical and genotypic characteristics. WES and Sanger Sequencing confirm the diagnosis of COXPD35; however, it can be challenging in resource-limited settings.