Exotropia in a Patient With a Novel Homozygous 4-Hydroxyphenylpyruvate Dioxygenase-Like Protein (HPDL) Variant

The 4-hydroxyphenylpyruvate dioxygenase-like protein (<i>HPDL</i>) is a mitochondria-localized protein involved in the biosynthesis of coenzyme Q10 in the electron transfer system, and its variants have been reported to cause progressive neurodegenerative diseases such as neonatal leukoencephalopathy and hereditary spastic paraplegia. In this case report, we present a case of a nine-year-old girl with exotropia with a novel <i>HPDL</i> variant who underwent strabismus surgery. She was referred to the ophthalmology department with exotropia and a history of progressive spastic paraplegia with gait disturbance. Brain MRI showed no remarkable findings. Whole-exome sequencing revealed a homozygous variant c.1040delC (p.Thr347Metfs*66) in the <i>HPDL</i> gene. Ophthalmic examination revealed a best-corrected visual acuity of 20/12 in both eyes. Fundoscopy showed retinal discoloration at the level of the retinal pigment epithelium in the right eye. As the patient had intermittent exotropia with good convergence, she was followed up conservatively. One year after the initial examination, the patient could not keep her eyes in a central position by convergence. The alternate prism cover test revealed exotropia of 80 prism diopters. We diagnosed that intermittent exotropia had deteriorated into constant exotropia. The patient's family requested a strabismus surgery, which was conducted under general anesthesia. Standard left lateral rectus recession, left medial rectus resection, and right lateral rectus recession were also performed. Postoperatively, her exotropia was reduced, and she achieved good convergence. The patient and her family were satisfied with the surgical outcome, and no recurrence was noted one year postoperatively. Our results provide important information for the associations of variant in <i>HPDL</i> with progressive spastic paraplegia, strabismus and retinal changes and broaden the genetic spectrum of HPDL-related disease. This is the first report to present a novel <i>HPDL</i> variant and document the performance of strabismus surgery for constant exotropia.