A phenotype without spasticity in sacsin-related ataxia

Abstract

The authors describe two Japanese siblings with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) without spasticity, usually a core feature of this disorder. They had a novel homozygous missense mutation (T987C) of the SACS gene, which resulted in a phenylalanine-to-serine substitution at amino acid residue 304.

Diagnostic Value of Neurophysiological Evaluation in Patients with ARSACS

“…The results of previous nerve conduction studies on ARSACS are summarized in Table 3 [6,9,11,12,[15][16][17][18][19][20][21][22][23]. Our findings along with those of previous studies, show that the electrophysiological features of peripheral neuropathy in ARSACS are the following: 1) a prolonged DML and reduced MCV with normal CMAPs in the upper-limb nerves, 2) absence Table 2 Results of nerve ultrasonographies in two patients with ARSACS.…”

“…After mapping and identification of the gene in patients with ARSACS, non-Quebecois families with ARSACS have been reported from Italy [3], Tunisia [4], Turkey [5], Spain [6], and Belgium [7], thus showing a worldwide occurrence. Since Ogawa and colleagues first reported a Japanese family with ARSACS with a missense mutation in 2004 [8], additional such families have been reported in Japan [9,10].…”

“…Although the clinical phenotype of the patients in Quebec is uniform, non-Quebecois cases including Japanese show phenotypic variability [1]. Especially in Japan, sacsin-related ataxia without spasticity and hyperreflexia has been reported [9,11,12]. These cases, lacking a core clinical feature of ARSACS, are sometimes difficult to diagnose.…”

“…These cases, lacking a core clinical feature of ARSACS, are sometimes difficult to diagnose. Severe peripheral nerve degeneration may mask any spasticity in these patients [9,11].…”

Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS): Clinical, Radiological and Epidemiological Aspects

“…In eastern France, ARSACS was identified in two index patients among 102 autosomal recessive cerebellar ataxia (ARCA) ones (Anheim et al, 2008), meanwhile among 43 Dutch ARCA patients, 16 with mutations in the SACS gene were identified (Vermeer et al, 2008). In Japan, 17 Japanese ARSACS families have been discovered on SACS gene analysis so far (Ogawa et al, 2004;Hara et al, 2005;Shimazaki et al, 2005;Yamamoto et al, 2005;Ouyang et al, 2006;Yamamoto et al, 2006;Okawa et al, 2006;Hara et al, 2007;Takado et al, 2007;Shimazaki et al, 2007;Kamada et al, 2008;Tsugawa et al, 2009;Haga et al, 2011;Miyatake et al, 2011;Komure et al, 2006). ARSACS might be the second most frequent ARCA next to ataxia with oculomotor apraxia 1 (AOA1) in Japan.…”