Objective: We propose a novel diagnostic algorithm to help clinicians to diagnose inborn errors of metabolism (IEM) in adolescents and adults that present with a movement disorder.

Background: IEM presenting in adults are still largely unexplored. Despite the fact that adult-onset phenotypes have been known for many years, little attention is given to these disorders in neurological training and daily practice, and many neurologists find diagnosing these disorders complicated. It is important to realize that the adult-onset presentation differs from childhood-onset phenotypes, often leading to considerable diagnostic delay. The identification of these patients at the earliest stage of disease is important, since early treatment may prevent or lessen further brain damage.

Method: We performed a systematic review of all papers that concerned movement disorders in late-onset IEM up to October 2017. Type of movement disorder, associated features, and findings during additional investigations were collected per IEM. Based on this systematic review, we propose a novel algorithm.

Results: Movement disorders were present in 35 late-onset IEM. These metabolic disorders form the basis of the algorithm. Detailed clinical phenotyping is the diagnostic cornerstone of the approach. An underlying IEM should be suspected in particular in patients with more than one movement disorder or in patients with other neurological, psychiatric, or systemic symptoms. Furthermore, family history can give an extra clue to an IEM, even as the existence of specific triggers. Drugs, toxic agents, and other acquired disorders as the cause of the movement disorders must be excluded. NGS is the first test of choice to confirm an IEM, whereas biochemical tests remain the first choice in acute-onset IEM.

Conclusion: We propose a novel diagnostic algorithm based on clinical phenotyping and NGS, in order to increase the recognition of IEM in adolescent and adult patients who present with a movement disorder. With the use of careful and systematic clinical phenotyping combined with novel diagnostic approaches such as NGS, the diagnostic yield of late-onset IEM will increase, in particular in patients with milder or unusual phenotypes.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/movement-disorders-in-late-onset-inborn-errors-of-metabolism-a-new-diagnostic-algorithm/