Metabolic Treatments of Cerebellar Ataxia

Abstract

Metabolic causes of cerebellar ataxia encompass all categories of inherited metabolic diseases, i.e., accumulation and deficiency of small or complex molecules, and disorders of energy metabolism. Patients may present with chronic cerebellar or spino-cerebellar ataxia, paroxysmal episodes of cerebellar ataxia, or myoclonic ataxia. In case of chronic cerebellar ataxia, a fast and simple metabolic screening can identify etiologies that are amenable to treatment, especially vitamin E, cerebrospinal fluid (CSF) glucose (or, in some countries, the newly developed METAglut1™), plasma cholestanol, very long-chain fatty acids, phytanic acid, and lysosphingomyelin-509. If magnetic resonance imaging (MRI) reveals an abnormal white matter, then the activities of arylsulfatase A and galactocerebrosidase should be measured. In case of paroxysmal episodes of cerebellar ataxia, CSF glucose (or METAglut1™), plasma lactate, pyruvate, ammonium, and amino acid chromatography are of utmost importance. Glucose transporter type 1 (Glut1) deficiency syndrome, cerebrotendinous xanthomatosis, ataxia related to vitamin E deficiency, and Refsum disease are among the most common causes of treatable cerebellar ataxia. Metabolic treatments range from dietary intervention and supplementation therapies to metabolite-lowering therapies, pharmacological chaperones, and replacement therapies.