Juan Darío Ortigoza-Escobar. A Proposed Diagnostic Algorithm for Inborn Errors of Metabolism Presenting With Movements Disorders. Published on 13 November 2020. Front. Neurol. doi: 10.3389/fneur.2020.582160
Inherited metabolic diseases or inborn errors of metabolism frequently manifest with both hyperkinetic (dystonia, chorea, myoclonus, ataxia, tremor, etc.) and hypokinetic (rigid-akinetic syndrome) movement disorders. The diagnosis of these diseases is in many cases difficult, because the same movement disorder can be caused by several diseases. Through a literature review, two hundred and thirty one inborn errors of metabolism presenting with movement disorders have been identified. Fifty-one percent of these diseases exhibits two or more movement disorders, of which ataxia and dystonia are the most frequent. Taking into account the wide range of these disorders, a methodical evaluation system needs to be stablished. This work proposes a six-step diagnostic algorithm for the identification of inborn errors of metabolism presenting with movement disorders comprising red flags, characterization of the movement disorders phenotype (type of movement disorder, age and nature of onset, distribution and temporal pattern) and other neurological and non-neurological signs, minimal biochemical investigation to diagnose treatable diseases, radiological patterns, genetic testing and ultimately, symptomatic, and disease-specific treatment. As a strong action, it is emphasized not to miss any treatable inborn error of metabolism through the algorithm.
Figure 3. Radiological patterns in selected inborn errors of metabolism. (A) Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency (ECHS1). MRI (T2W) showing bilateral symmetric signal hyperintensity in globus pallidus and a small cavitation in the left globus pallidus. (B) Type 3 Gaucher disease (GBA). MRI (T1W) showing decrease volume of white matter and hydrocephalus. (C) Glutaric aciduria type 1 (GCDH). MRI (T2 FSE) showing bilateral symmetric signal hyperintensity in putamen and globus pallidus and posterior periventricular white matter abnormalities. (D) Rhizomelic chondrodysplasia punctata, type 1 (PEX7). MRI (T2) showing bilateral symmetric posterior periventricular white matter hyperintensity and ventriculomegaly. (E,F) L-2-hydroxyglutaric aciduria (L2HGA). MRI (T2 and FLAIR) showing bilateral diffuse cerebral white matter and dentate nuclei hyperintensities. (G) Methylmalonic aciduria and homocystinuria, cblC type (MMACHC). MRI (T1) showing a very thin corpus callosum. (H) Aicardi-Goutières syndrome 2 (RNASEH2B). CT showing multiple calcifications in basal ganglia.