Ataxia and Extrapyramidal Movement Disorders
- An insight into the biochemistry of inborn errors of metabolism for a clinical neurologist

Extrapyramidal movement disorders in patients with inherited neurometabolic disorders are almost always associated with neurological signs referable to other parts of the nervous system. Progressive ataxia may be the presenting symptom in many late-onset lysosomal storage disorders (late-onset metachromatic leukodystrophy, Krabbe disease, galactosialidosis, GM 2 gangliosidosis and Niemann-Pick type C), abetalipoproteinemia, mitochondrial electron transport chain defects, neuronal ceroid lipofuscinosis, Refsum disease and Hartnup disease.[6] L-2-Hydroxyglutaric aciduria is a newly identified metabolic disorder, which can present with ataxia and macrocephaly in adulthood.[7],[8] Differentiation from nonmetabolic hereditary ataxias is usually possible due to the presence of other neurological signs such as psychomotor retardation and evidence of nonneurological involvement with the disease. All patients with recurrent episodes of ataxia separated by symptom-free intervals should be investigated for a possible metabolic disorder. Intermittent ataxia is a common manifestation of metabolic decompensation in urea cycle enzyme defects, organic acidopathies, maple syrup urine disease variants, and pyruvate dehydrogenase deficiency.[9] The simple biochemical differentiation of these defects,[3] is given in [Table 2].

Extrapyramidal signs are an important manifestation of childhood neurometabolic disorders.[10],[11] Glutaric aciduria should be high on priority in the differential diagnosis in children with acute profound dyskinesia or subacute motor delay accompanied by severe choreoathetosis and dystonia.[12] In methylmalonic and propionic acidemias, there can be late-onset extra pyramidal disease.[13] Choreoathetosis is characteristically observed in Lesch-Nyhan syndrome and should be a diagnostic consideration in boys who present with predominant extrapyramidal signs in the second year of life. In addition, it may sometimes present with athetosis without cognitive impairment or behavioral abnormalities in adulthood.[14] Parkinsonism More Details and dystonia are the prominent features in many patients with Wilson disease. Dystonia of the extremities growing worse during the course of the day with normal intellect and a dramatic response to treatment with l-dopa is characteristic of Segawa syndrome,[15] Lysosomal storage disorders that can present with dystonia include Niemann-Pick disease type C,[16],[17] Gaucher disease type 3, GM2 gangliosidosis[18],[19] and GM1 gangliosidosis.[20],[21]

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