An overview of the most common autosomal recessive cerebellar ataxias is presented by researchers at the UCLA Ataxia Center, Los Angeles. Friedreich’s ataxia-like syndromes include FA (involving mitochondrial iron metabolism), ataxia with vitamin-E deficiency (vitamin E homeostasis), abetalipoproteinemia (lipoprotein metabolism), and Refsum’s disease (peroxisomal disease). FA-like with cerebellar atrophy syndromes: late-onset Tay-Sachs disease (a G-gangliosidosis with deficiency of B-hexosaminidase A), cerebrotendinous xanthomatosis (deficiency of mitochondrial enzyme sterol 27-hydroxylase involved with bile-acid synthesis), DNA polymerase g disorder (mitochondrial recessive ataxia syndrome), and spinocerebellar ataxia with axonal neuropathy. Early-onset ataxia with cerebellar atrophy: ataxia telangiectasia; ataxia with oculomotor apraxia types 1 and 2, caused by mutations of the aprataxin and senataxin genes; ataxia of Charlevoix-Saquenay (sacsin gene); infantile-onset spinocerebellar ataxia (a gene encoding the proteins twinkle and twinky); Cayman ataxia (gene encoding caytaxin); and Marinesco-Sjogren syndrome (rare infantile-or childhood-onset ataxia, with cataracts, mental retardation, myopathy, hypogonadotropic hypogonadism, and skeletal deformities). Friedreich ataxia is the most prevalent, and directed genetic testing is recommended based on clinical phenotype, which avoids the expense of an unfocussed molecular diagnostic battery. [1]
COMMENT. Hereditary ataxias are autosomal dominant, autosomal recessive, X-linked, and mitochondrial. The clinical phenotype is important in the differentiation of these ataxias, especially when a characteristic family history is unavailable. Neuroimaging is also useful to differentiate ataxias with and without cerebellar atrophy.
Cerebellar ataxia in Norway. Among 60 individuals from 39 families with ataxia, age at onset was lower for patients with autosomal recessive (ARCA) compared with autosomal dominant cerebellar ataxias (ADCA). Disease prevalence in Oslo is estimated at 2.2/100,000 for ARCA and 3.0/100,000 for ADCA. Surprisingly, no Norwegian family with Friedreich ataxia was found in the patients referred to a Department of Neurology in Oslo. Pediatric patients may have been treated elsewhere. [2]