Autosomal recessive spastic ataxia of Charlevoix-Saguenay: a family report from South Brazil

Abstract

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset, neurodegenerative disorder caused by mutations in SACS, firstly reported in Quebec, Canada. The disorder is typically characterized by childhood onset ataxia, spasticity, neuropathy and retinal hypermyelination. The clinical picture of patients born outside Quebec, however, is often atypical. In the present article, the authors describe clinical and neuroradiological findings that raised the suspicion of an ARSACS diagnosis in two female cousins with Germanic background from Rio Grande do Sul, Brazil. We present a review on the neuroimaging, ophthalmologic and neurophysiologic clues for ARSACS diagnosis. The early-onset, slowly progressive, spastic-ataxia phenotype of reported patients was similar to ARSACS patients from Quebec. The SACS sequencing revealed the novel homozygous c.5150_5151insA frameshift mutation confirming the ARSACS diagnosis. ARSACS is a frequent cause of early onset ataxia/spastic-ataxia worldwide, with unknown frequency in Brazil.

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

“…Patients presented early-onset and slow progressive spastic ataxia. Retinal and nerve conduction abnormalities were also prominent [ 117 ]. In 2019, 13 Brazilian patients were investigated with ARSACS, who presented ataxia, spasticity and retinal nerve fiber thickening.…”

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

“…Some foot deformities are also reported in ARSACS, such as pes cavus, hammer toes and foot drop, without clear prevalence [ 1 – 3 , 5 – 7 , 9 , 12 , 13 , 22 , 23 , 27 , 30 , 34 , 38 – 40 , 52 , 55 , 56 , 59 , 62 – 64 , 66 , 69 , 72 , 74 , 78 , 79 , 81 , 91 , 93 , 95 , 96 , 99 – 102 , 106 , 107 , 109 , 110 , 115 , 116 , 120 , 122 , 129 , 136 , 137 , 141 ]. Only 2/12 participants reported foot deformities that impacted their life.…”

“…Balance difficulties are clearly reported in the literature [ 1 – 3 , 5 , 12 , 13 , 19 , 22 , 28 , 36 , 46 , 48 , 49 , 59 , 64 , 71 , 76 , 78 – 80 , 83 , 87 , 89 , 99 , 106 , 116 , 117 , 119 , 123 , 133 , 140 , 141 , 143 , 144 ]. Almost all participants reported experiencing problems with balance.…”

“…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.…”

“…A wide range of dysarthria severity (mild to severe) are documented [ 2 – 7 , 9 – 13 , 15 , 16 , 18 , 20 , 22 , 27 , 28 , 30 , 34 , 38 – 40 , 51 , 53 , 56 , 57 , 59 , 60 , 62 – 64 , 66 , 67 , 69 , 71 , 72 , 74 , 79 , 80 , 82 , 83 , 85 , 87 , 89 , 91 , 92 , 95 , 99 , 101 – 103 , 110 , 112 , 113 , 116 , 117 , 119 , 120 , 122 – 124 , 127 – 129 , 131 – 134 , 136 – 141 , 144 ]. The authors described dysarthria in terms of slurred or unclear speech [ 3 , 22 , 66 , 87 , 103 , 134 ], delay in speech production [ 140 ], and slow speech [ 141 , 144 ]. Among the participants, 5/12 noted di...…”