Case Report: Expanding the Genetic and Phenotypic Spectrum of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay

Parham Habibzadeh,Muhammad Mahdi Nashatizadeh,Soroor Inaloo,Mohammad Ali Faghihi,Matthis Synofzik,Vahid Reza Ostovan,Zahra Tabatabaei

doi:10.3389/fgene.2020.585136

Abstract

Autosomal recessive spastic ataxia of Charlevoix–Saguenay (ARSACS) is a rare neurodegenerative disorder caused by biallelic mutations in the SACS gene. Once thought to be limited to Charlevoix–Saguenay region of Quebec, recent evidence has indicated that this disorder is present worldwide. It is classically characterized by the triad of ataxia, pyramidal involvement, and axonal-demyelinating sensorimotor neuropathy. However, diverse clinical features have been reported to be associated with this disorder. In this report, we present the first Iranian family affected by ARSACS with unique clinical features (mirror movements, hypokinesia/bradykinesia, and rigidity) harboring a novel deletion mutation in the SACS gene. Our findings expand the genetic and phenotypic spectrum of this disorder.

Highlights

First reported in the late 1970s, autosomal recessive spastic ataxia of Charlevoix–Saguenay (ARSACS; MIM#270550) is a neurodegenerative disorder characterized by early-onset spastic ataxia and sensorimotor neuropathy (Bouchard et al, 1978; Pilliod et al, 2015)
Mild rigidity after activation maneuvers (Supplementary Video 1), mirror movements (Supplementary Video 2), hypokinesia (Supplementary Video 3), and dysmetria were noticed in both upper extremities, predominantly on the left side
Autosomal recessive cerebellar ataxias constitute a heterogeneous group of disorders from both clinical and genetic perspectives (Beaudin et al, 2019; Synofzik et al, 2019)

Summary

BACKGROUND

First reported in the late 1970s, autosomal recessive spastic ataxia of Charlevoix–Saguenay (ARSACS; MIM#270550) is a neurodegenerative disorder characterized by early-onset spastic ataxia and sensorimotor neuropathy (Bouchard et al, 1978; Pilliod et al, 2015). ARSACS is caused by pathogenic mutations in SACS gene (OMIM #604490), coding for a 520-kDa multidomain protein called sacsin, which is thought to integrate the 70-kDa heat shock protein (Hsp70) chaperone and ubiquitin–proteasome systems. Sacsin is most highly expressed in large neurons involved in the motor system, especially cerebellar Purkinje cells, where it has normally been found to protect against at least one mutation of the ataxin-1 gene that results in spinocerebellar ataxia type 1. We report on a novel homozygous SACS mutation in an Iranian family with ARSACS with unique clinical findings

Clinical Findings

Molecular Findings

DISCUSSION

ETHICS STATEMENT