Treatable Inherited Movement Disorders in Children: Spotlight on Clinical and Biochemical Features

Background: About 80% of monogenic metabolic diseases causing movement disorders (MDs) emerges during the first 2 decades of life, and a number of these conditions offers the opportunity of a disease-modifying treatment. The implementation of enlarged neonatal screening programs and the impressive rapid increase of the identification of new conditions are enhancing our potential to recognize and treat several diseases causing MDs, changing their outcome and phenotypic spectrum. Methods and Findings: A literature review of monogenic disorders causing MDs amenable to treatment was conducted focusing on early clinical signs and diagnostic biomarkers. A classification in 3 broad categories based on the therapeutic approach has been proposed. Some disorders result in irreversible neurotoxic lesions that can only be prevented if treated in a presymptomatic stage, and others present with a progressive neurological impairment that a timely diagnosis and treatment may reverse or improve. Some MDs are the result of the failure of intracellular energy supply or altered glucose transport. The treatment in these conditions includes vitamins or a metabolic shift from a carbohydrate to a fatty acid catabolism, respectively. Finally, a group of highly treatable MDs are the result of defects of neurotransmitter metabolism. In these disorders, the supplementation of precursors or mimetics of neurotransmitters can deeply change the disease natural history. Conclusions: To prevent serious and irreversible neurological impairment, the diagnostic work-up of MDs in children should consider a number of clinical red flags and biomarkers denoting specifically treatable diseases.