Ataxia with oculomotor apraxia type 2: a clinical and genetic study of 19 patients.
Ataxia with oculo-motor apraxia type 2 (AOA2) is a recently described autosomal recessive cerebellar ataxia (ARCA) caused by mutations in the senataxin gene (SETX). We analysed the phenotypic spectrum of 19 AOA2 patients with mutations in SETX, which seems to be the third most frequent form of ARCA in Algeria after Freidreich ataxia and Ataxia with vitamin E deficiency. In AOA2 patients, the mean age at onset for all families was in the second decade. Cerebellar ataxia was progressive, slowly leading to disability which was aggravated by axonal polyneuropathy present in almost all the patients. Mean disease duration until wheelchair was around 20 years. Oculo-motor apraxia (OMA) was present in 32% of the patients while convergent strabismus was present in 37%. Strabismus is therefore also very suggestive of AOA2 when associated with ataxia and polyneuropathy even in the absence of OMA. Cerebellar atrophy was more severe in the eldest patients; however it may also be an early sign since it was present in the youngest and paucisymptomatic patients. The initial sign was gait ataxia in all but two patients who presented with head tremor and writer cramp, respectively. Serum alpha-fetoprotein, which was elevated in all tested patients, was a good marker to suggest molecular studies of the SETX gene.
Tazir
M
M
Laboratoire de Neurosciences, Université d'Alger, Service de Neurologie, Centre Hospitalier Universitaire Mustapha, Alger, Algeria. meriemtazir@yahoo.com
Ali-Pacha
L
L
M'Zahem
A
A
Delaunoy
J P
JP
Fritsch
M
M
Nouioua
S
S
Benhassine
T
T
Assami
S
S
Grid
D
D
Vallat
J M
JM
Hamri
A
A
Koenig
M
M
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001072:Apraxias / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D001284:Atrophy; D002524:Cerebellar Ataxia / Q000150:complications* / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D002531:Cerebellum / Q000473:pathology / Q000503:physiopathology; D004265:DNA Helicases; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D064251:Multifunctional Enzymes; D009154:Mutation; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009431:Neural Conduction; D015835:Ocular Motility Disorders / Q000150:complications* / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D010375:Pedigree; D010641:Phenotype; D020365:RNA Helicases / Q000235:genetics*; D055815:Young Adult; D000509:alpha-Fetoproteins / Q000032:analysis
D064251:Multifunctional Enzymes; D000509:alpha-Fetoproteins; C484368:SETX protein, human; D004265:DNA Helicases; D020365:RNA Helicases