Movement disorders and eye movement disorders in late-onset inborn errors of metabolism

Abstract

This thesis is about late-onset inborn error of metabolism (IEM). IEMs are genetic disorders that cause disturbance of a biochemical process in the body. Some of these disorders are detected through neonatal screening, however, this is not available for the majority. For a long time, these disorders were considered to occur only in children, but after improvement of diagnostic methods, IEMs are found to be present in adolescents and adults as well. Unfortunately, it often takes a long time before these patients get the right diagnosis, which is a problem because some IEMs are treatable. In this thesis, tools to enhance the recognition of IEMs are provided. First, a new diagnostic approach is presented to improve the detection of late-onset IEMs presenting with a movement disorder, in which clinical phenotyping is the cornerstone. An underlying IEM should be suspected in patients with movement disorders, psychiatric symptoms, and cognitive impairment. Eye movement disorders are frequent too, and this thesis shows that they can be present early in the disease course and may be very characteristic. To aid non-neurologists to recognize movement disorders, which is important because they can serve as a clue in the diagnosis of an IEM and they impact quality of life, a diagnostic screening tool is presented.To conclude, this thesis contributes to a clearer view of late-onset IEMs. It gives tools to enhance clinical diagnosis and suggestions for improvement of care. This is both important in the light of the development of new treatments for IEMs.