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Chapter 9 - Movement disorders in childhood metabolic diseases

from Section II - Movement disorders in systemic disease

Published online by Cambridge University Press:  05 April 2014

By
Emilio Fernández-Álvarez  and
Agathe Roubertie
Edited by
Werner Poewe  and
Joseph Jankovic
Emilio Fernández-Álvarez
Affiliation:
Department of Neurology, Hospital San Juan de Dios, Barcelona, Spain
Agathe Roubertie
Affiliation:
Department of Neurology, Hôpital Gui de Chauliac, Montpellier, France
Werner Poewe
Affiliation:
Medical University Innsbruck
Joseph Jankovic
Affiliation:
Baylor College of Medicine, Texas
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Summary

Definitions and classification

Inborn errors of metabolism (IEM) represent a vast, diverse, and heterogeneous collection of disorders in which there is a block at some point in the normal metabolic pathway caused by a genetic defect of a specific enzyme. Up to now, more than 500 IEM have been characterized: the great majority are autosomal recessive. Broadly, these IEM may be divided into three groups (Saudubray et al. 2006):

  • Group 1: Disorders that give rise to an acute or chronic intoxication. It encompasses aminoacidopathies, organic acidurias, urea cycle disorders, sugar intolerances, metal disorders, and porphyrias. This group also includes inborn errors of neurotransmitter synthesis and catabolism, especially monoamine metabolism defects. The disorders included in group 1 share common features: no interference with embryo-fetal development, presentation after a symptom-free interval with chronic or intermittent manifestations sometimes triggered by provoking factors (for example, stress fever, intercurrent illness). Most of these disorders are treatable and require an emergency removal of the toxin by special diets, extracorporeal procedures, cleansing drugs, or vitamins.

  • Group 2: Disorders involving energy metabolism. This group includes inborn errors of intermediary metabolism that affect mitochondrial energetic processes (respiratory chain disorders, Krebs cycle and pyruvate oxidation defects, fatty acid oxidation disorders) and the cytoplasmic defects of energy metabolism (glucose transport defect, glycolysis, glycogenosis, gluconeogenesis, hyperinsulinisms, and creatine and pentose phosphate pathways). Some of these disorders might interfere with the embryo-fetal development; they give rise to chronic manifestations, sometimes associated with paroxysmal symptoms. Some of these disorders are partly treatable.

  • Group 3: Disorders involving complex molecules. This group involves cellular organelles and cellular trafficking and processing of complex molecules; it includes lysosomal, peroxisomal, glycosylation, and cholesterol synthesis defects. Symptoms are permanent, progressive, and independent of intercurrent events. Enzyme replacement therapy or bone marrow transplantation are indicated in some lysosomal storage diseases.

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Movement Disorders in Neurologic and Systemic Disease , pp. 115 - 130
Publisher: Cambridge University Press
Print publication year: 2014

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