The mind’s eye: A neuro-ophthalmological perspective on Niemann-Pick type C disease

Niemann-Pick disease type C (NPC) is a rare autosomal recessive genetic disease caused by mutations in the NPC1 and NPC2 genes with an estimated incidence of 1:120 000 live births. The clinical presentations vary across the ages. Children present with visceral symptoms related to cholesterol accumulation in the liver and adults have predominantly neuropsychiatric features such as dementia. However, vertical supranuclear gaze palsy can be present from the first year of life and is a strong feature in the diagnosis of NPC, which can be confirmed by a skin biopsy. A 36-year-old female with long-standing depression was referred for an evaluation of dystonia. She had progressive cognitive decline, dysarthria, dysphonia, dystonia of the trunk and limbs, ataxia and supranuclear gaze palsy. A similar course of illness affected her brother. Her parents were first cousins. She had positive Filipin stain of fibroblasts cultured from her skin biopsy, confirming the diagnosis of NPC. Miglustat, the approved drug for treatment, was not accessible. She had been on simvastatin since diagnosis, with a poor response, and had ongoing severe cognitive and physical disability. There are few conditions that present with neuropsychiatric symptoms and supranuclear gaze palsy. This patient had been managed as chronic depression with psychosis since her teenage years and her diagnosis was reviewed only when she had developed dystonia. Supranuclear gaze palsy is an early diagnostic clinical clue that could be present from infancy and should be sought in patients with neurocognitive presentations.