Early onset cerebellar ataxia – recessive and autosomaldominant forms (Part II)

Abstract

Early cerebellar ataxias (autosomal recessive and autosomal dominant) are a heterogeneous group of neurodegenerative diseases, characterized by cerebellar dysfunction. Autosomal recessive (AR) cerebellar degenerative ataxias with early onset are the most common AR ataxias in childhood. Friedrich's ataxia is a complex, multisystem disease caused by a GAA triplet repeat expansion in the FXN gene. As a result a deficiency of frataxin occurs, leading to a disturbance in mitochondrial iron homeostasis and an increase in oxidative stress. Degenerative changes occur in the cells of the spinal cord and cerebellum, to a lesser extent in the cerebral cortex, as well as in the heart and skeletal muscle cells, liver and pancreas. Initial symptoms include progressive spinocerebellar ataxia, hypo- to areflexia for the knee and Achilles reflexes, and a positive Babinski sign. With progression other symptoms of the central and peripheral nervous system are added, cardiomyopathy, scoliosis and pes cavus develop and an impaired glucose tolerance is observed. The differential diagnosis of cerebellar degenerative diseases in childhood includes malformations in the development of the cerebellum and posterior cranial fossa, persistent neuroinfections with subacute course, neurolipidosis and leukodystrophy. To date, there is no effective treatment for cerebellar degenerative diseases. Gene therapy in Friedreich's ataxia is studied, attempts are being made to influence the course of the disease using iron chelators, antioxidants, modulators of the inflammatory process. Autosomal dominant ataxias occur less often in childhood. They are a heterogeneous group of diseases that presents only with cerebellar ataxia or in combination with symptoms due to damage of the basal ganglia, cerebral cortex, optic nerves, ponto-medullary system, spinal tract and peripheral nervous system.