ABSTRACT
Whether the recessive ataxias, Ataxia with oculomotor apraxia type 1 (AOA1) and 2 (AOA2) and Ataxia telangiectasia (AT), can be distinguished by video-oculography and alpha-fetoprotein level remains unknown. We compared 40 patients with AOA1, AOA2 and AT, consecutively referred between 2008 and 2015 with 17 healthy subjects. Video-oculography revealed constant impairments in patients such as cerebellar signs, altered fixation, impaired pursuit, hypometric saccades and abnormal antisaccades. Horizontal saccade latencies could be highly increased reflecting oculomotor apraxia in one third of patients. Specific distinctive alpha-fetoprotein thresholds were determined for AOA1 (7-15 µg/L), AOA2 (15-65 µg/L) and AT (>65 µg/L). Early age onset, severe walking disability, movement disorders, sensori-motor neuropathy and cerebellar atrophy were all shared. In conclusion, alpha-fetoprotein level seems to permit a distinction while video-oculography does not and therefore is not mandatory, even if an appropriate oculomotor examination remains crucial. Our findings are that AOA1, AOA2 and AT form a particular group characterized by ataxia with complex oculomotor disturbances and elevated AFP for which the final diagnosis is relying on genetic analysis. These findings could guide genetic analysis, assist reverse-phenotyping and provide background for the interpretation of the numerous variants of unknown significance provided by next-generation sequencing.
Subject(s)
Apraxias/congenital , Ataxia Telangiectasia/blood , Ataxia Telangiectasia/diagnostic imaging , Cogan Syndrome/blood , Cogan Syndrome/diagnostic imaging , Multimodal Imaging , alpha-Fetoproteins/metabolism , Adolescent , Adult , Apraxias/blood , Apraxias/diagnostic imaging , Apraxias/genetics , Ataxia Telangiectasia/genetics , Child , Child, Preschool , Cogan Syndrome/genetics , Female , Humans , Male , Middle Aged , alpha-Fetoproteins/geneticsSubject(s)
Brain/pathology , Consciousness Disorders/etiology , Hypoglycemia/diagnosis , Magnetic Resonance Imaging , Quadriplegia/etiology , Aged, 80 and over , Apraxias/blood , Apraxias/etiology , Consciousness Disorders/blood , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diagnosis, Differential , Diagnostic Errors , Dysarthria/blood , Dysarthria/etiology , Female , Humans , Hypoglycemia/complications , Imaging, Three-Dimensional , Insulin/therapeutic use , Quadriplegia/blood , Stroke/diagnosisABSTRACT
Ataxia with oculomotor apraxia type 2 (AOA2), a neurodegenerative disorder with juvenile to adolescent onset is caused by mutations within the SENATAXIN gene ( SETX). We performed molecular analyses in six patients showing clinically an AOA2 phenotype and moderate to significant elevated serum alpha-fetoprotein levels. Sequencing the 24 coding exons and flanking intronic sequences revealed 11 novel DNA variations, including seven unknown missense mutations, a dinucleotide deletion, a four-nucleotide deletion affecting the 5' splice site of exon 22 and two sequence variations, which are considered to be polymorphisms. By molecular testing the clinical diagnosis has been confirmed in all patients.
Subject(s)
Apraxias/genetics , Cerebellar Ataxia/genetics , DNA Mutational Analysis , Oculomotor Nerve Diseases/genetics , RNA Helicases/genetics , alpha-Fetoproteins/metabolism , Adolescent , Adult , Alleles , Apraxias/blood , Apraxias/diagnosis , Atrophy , Cerebellar Ataxia/blood , Cerebellar Ataxia/diagnosis , Cerebellum/pathology , Chromosome Deletion , Consanguinity , DNA Helicases , Exons/genetics , Female , Follow-Up Studies , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Multifunctional Enzymes , Mutation, Missense , Neurologic Examination , Oculomotor Nerve Diseases/blood , Phenotype , Polymorphism, Genetic/genetics , Young AdultSubject(s)
Apraxias/etiology , Blood Glucose/metabolism , Hypoglycemia/complications , Apraxias/blood , Chronic Disease , Humans , Hypoglycemia/diagnosis , Male , Middle AgedABSTRACT
A 57-year-old man on long-term renal dialysis presented with speech dyspraxia, a symptom characteristic of early aluminium encephalopathy. Once fully developed, this condition has a poor prognosis despite deferoxamine (DFO) treatment.
