Coexistence of Hereditary Spastic Paraplegia Type 4 and Narcolepsy: A Case Report

Abstract

Spastic paraplegia type 4 (SPG4) is the most common type of hereditary spastic paraplegia (HSP) caused by the mutations in the <i>SPAST</i> gene, which encodes a microtubule-severing protein named spastin. Spastin regulates the number and mobility of microtubules and is essential for axonal outgrowth and neuronal morphogenesis. Herein, we report a patient with SPG4 harboring a novel donor splice site mutation in the <i>SPAST</i> gene (c.1616+1dupG). Although SPG4 usually manifests itself as a pure form of HSP, this patient exhibited a slow progressive cognitive decline and also developed narcolepsy type 2 (narcolepsy without cataplexy) prior to the onset of SPG4. Recently, cognitive decline has attracted attention as a main non-motor symptom of SPG4. However, this is the first reported case of a patient developing both SPG4 and narcolepsy, although it remains unclear whether the manifestation of the two diseases is a coincidence or an association. In this report, we describe the clinical symptoms and genetic background of the patient.

A case of monozygotic twins with hereditary spastic paraplegia type 4 and epilepsy, of whom only one developed narcolepsy type 1

“…Regarding the association between narcolepsy and SPG4, only one case of SPG4 with NT2 has been reported (Nagai et al, 2021), although this case of NT2 was diagnosed without a MSLT and CSF orexin levels. Our report is the first case of SPG4 with NT1.…”