Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay without Spasticity

Abstract

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare progressive neurodegenerative disease caused by either homozygous or compound heterozygous mutations in the SACS gene. The original ARSACS cases found in Quebec showed very homogenous phenotypes characterized by cerebellar ataxia, spasticity, and polyneuropathy. However, many cases with atypical phenotypes have been found in other regions and ethnic groups. We herein present a Japanese patient with atypical ARSACS who showed cerebellar ataxia and polyneuropathy, but no spasticity. She carried novel compound heterozygous mutations (p.Lys4326 Glu and p.Leu1412Lysfs*16) in the SACS gene. The brain MRI findings were useful for making a diagnosis of ARSACS.

Documenting manifestations and impacts of recessive ataxia to develop patient-reported outcome.

“…For people with ARSACS, there is a progressive loss of mobility that led to di culty or incapacity to run that began in childhood (33,34,40,68,73,87,96,111). Thus, it brings di culties to perform sports, like team sports or gymnastic (49,58,71,87,96). As it been seen before, people in the study report di culties to do physical activities in relation to their physical impairment like incoordination and loss of balance.…”

“…There are several functions that are affected by ARSACS: lower limbs, upper limbs, balance, strength, coordination, bladder and bowel functions, sexual functions, dysarthria, eye function, dysphagia, physical activities, and ADLs.Lower limbs and mobility. Even if the literature in ARSACS is scarce, several papers report impaired walking(31)(32)(33)(34), progressive loss of mobility(7, 32, 39, 53, 55-57, 60, 62-75) and the need to use a walking aid early on and progressively move on to a wheelchair(32,35, 38,40,41,45, 46,52,57, 65, 68, 69,71,72,74,(76)(77)(78)(79)(80)(81)(82)(83)(84)(85)(86)(87)). In the sample, 8/12 participants report impacts of this progressive loss of mobility.…”

Genetics of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) and Role of Sacsin in Neurodegeneration

“…Although she revealed the typical phenotype, it appeared to be milder than the typical ARSACS phenotypes. She did not present spasticity upon neurological examination, and the polyneuropathy was also missing [ 87 , 88 ].…”

Documenting manifestations and impacts of autosomal recessive spastic ataxia of Charlevoix–Saguenay to develop patient-reported outcome

“…Even if the literature in ARSACS is scarce, several papers report impaired walking [ 1 – 3 , 19 , 20 , 23 , 27 , 28 , 36 , 56 , 57 , 59 , 60 , 66 , 72 , 79 – 81 , 83 , 87 , 91 , 102 , 103 , 106 , 107 , 116 , 117 , 135 , 140 , 143 ], progressive loss of mobility [ 4 , 12 , 14 , 15 , 28 , 40 , 46 , 48 , 49 , 52 , 56 , 72 , 76 , 102 , 103 , 113 , 116 , 117 , 119 , 120 , 123 , 128 , 131 ] and the need to use a walking aid early on and progressively move on to a wheelchair [ 4 , 5 , 7 , 19 , 20 , 46 , 48 , 49 , 51 , 60 , 63 , 64 , 66 , 74 , 76 , 77 , ...…”

“…Even if strength seems normal for affected children, progressive and variable disabilities in strength are seen in ARSACS [ 19 , 20 , 47 , 111 , 141 ], in addition to muscle atrophy and weakness that affect both upper and lower limbs [ 1 , 4 – 7 , 9 , 13 , 20 , 22 , 23 , 27 , 36 , 46 – 49 , 52 , 54 – 56 , 63 , 66 , 69 , 71 , 74 , 78 , 79 , 82 , 83 , 87 , 93 , 99 , 100 , 102 , 104 , 106 , 109 – 111 , 117 , 121 , 122 , 129 , 131 , 136 , 137 , 143 , 144 ]. Data showed that 8/12 participants reported muscle weakness, particularly in the legs, ankles, and hands.…”