Kufor-Rakeb syndrome-associated psychosis: a novel loss-of-function ATP13A2 variant and response to antipsychotic therapy

Key Question

What is Kufor-Rakeb syndrome?

Kufor-Rakeb syndrome is a rare, autosomal recessive form of juvenile-onset parkinsonism caused by biallelic pathogenic variants in the ATP13A2 gene. It is characterized by motor symptoms such as parkinsonism, as well as neurological and psychiatric symptoms, including supranuclear gaze palsy, cognitive decline, and psychosis.

What role does the ATP13A2 gene play in Kufor-Rakeb syndrome?

The ATP13A2 gene encodes for the ATPase 13A2 protein, which functions as a polyamine transporter in late endolysosomes. Loss-of-function variants in this gene disrupt polyamine homeostasis, leading to the neurological and psychiatric manifestations observed in Kufor-Rakeb syndrome.

How is psychosis managed in patients with Kufor-Rakeb syndrome?

The study reports that quetiapine, an antipsychotic medication with a lower propensity to cause extrapyramidal symptoms, was effective in managing psychosis in a patient with Kufor-Rakeb syndrome. The patient exhibited a good response to quetiapine monotherapy and tolerated it well.

What are the clinical features of Kufor-Rakeb syndrome?

Clinical features of Kufor-Rakeb syndrome include juvenile-onset parkinsonism, facial-faucial-finger myoclonus, supranuclear gaze palsy, oculogyric dystonic spasms, dementia, and various neuropsychiatric symptoms, including psychosis.

What is the significance of the novel ATP13A2 variant identified in the study?

The study identified a novel loss-of-function ATP13A2 variant (c.1970_1975del) in a patient with Kufor-Rakeb syndrome-associated psychosis. This finding expands the spectrum of known ATP13A2 variants associated with the syndrome and provides insights into the genetic underpinnings of the disease.

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