A 42-year-old-male with history of Gout, Juvenile Myoclonic Epilepsy and learning disability.  He was adopted, due to consanguinity of biological parents. He presented with right-sided-facial drooping noticed while being shaved by his mother.

Physical exam revealed short stature, large head, low-set ears, hearing loss in the left ear compared to the right, optic nerve asymmetry.  Neurological examination showed peripheral cranial nerve VII palsy without other focal deficits.

Non-contrast-CT head revealed advanced white matter disease. MRI, showed punctate acute infarcts in the centrum semiovale and corona radiata, consistent with watershed infarcts. Also diffuse T2 hyperintensities, suspicious for leukodystrophy. Stroke workup revealed DRVVT of 2.03, concerning for APS. Warfarin started. Genetic testing revealed Ribose-5-phosphatase isomerase deficiency.

RPI deficiency is an autosomal recessive disorder that presents with progressive white matter changes, epilepsy, spasticity, and neurodevelopmental delays, often accompanied by ocular and auditory findings such as retinitis pigmentosa and hearing loss. In this case, the stroke-like presentation and advanced white matter disease were initially attributed to APS, as evidenced by the DRVVT. However, genetic testing revealed the underlying metabolic disorder, explaining the patient’s progressive leukodystrophy, hearing loss, and optic nerve asymmetry. This case illustrates the complexity of diagnosing rare metabolic disorders in the presence of more common conditions like APS, and the importance of considering genetic causes when faced with unusual neurological presentations and imaging findings.