Metabolic Disorders

Inborn errors of metabolism (IEM) are individually rare but have a collective incidence of approximately one in 1000. Most IEM can manifest with neurologic symptoms. It is crucial for the pediatric neurologist to be familiar with the evaluation and management of these disorders because many are amenable to specific treatments. This review provides a category-based approach to the diagnosis and treatment of IEM organized by metabolic pathway and organelle. Categories include disorders of mitochondrial fatty acid oxidation and carnitine metabolism, urea cycle disorders, organic acidemias, aminoacidopathies, lysosomal disorders, peroxisomal disorders, vitamin- and diet-responsive metabolic epilepsies, and neurotransmitter disorders. Multiple summary tables for quick reference are provided. Figures show mitochondrial β-oxidation and carnitine cycle; urea cycle; T2-weighted magnetic resonance images (MRI) of ornithine transcarbamylase deficiency presenting with hyperammonemic encephalopathy, propionic academia, methylmalonic academia, glutaric acidemia type 1, ethylmalonic encephalopathy, mitochondrial complex 1 deficiency, pyruvate dehydrogenase complex E3 deficiency, untreated biotin-thiamine-responsive basal ganglia disease, homocysteinemia and low plasma methionine (suspected remethylation defect), attenuated Krabbe disease, Hunter syndrome, and GM1-gangliosidosis; branched-chain amino acid catabolic pathway; lysine, hydroxylysine, and tryptophan catabolic pathway; intracellular cobalamin metabolism; metabolism of homocysteine; diffusion-weighted imaging of maple syrup urine disease, nonketotic hyperglycinemia, and poorly controlled phenylketonuria; sphingolipid metabolic pathway; skeletal surveys of Hurler syndrome demonstrating features of dysostosis multiplex and rhizomelic chondrodysplasia punctata type 1; MRI of Salla disease; peroxisomal oxidation reactions, and the biogenic amine biosynthetic pathway. Tables list fatty acid oxidation and carnitine disorders, metabolic myopathies presenting with recurrent rhabdomyolysis, urea cycle disorders, organic acidemias, IEM associated with abnormal head size, cobalamin disorders, aminoacidopathies, IEM associated with abnormal odor, lysosomal disorders, lysosomal disease Symptom categories (Not mutually exclusive), peroxisomal disorders, IEM associated with brain malformations, vitamin- and diet-responsive epilepsies, neurotransmitter disorders, and IEM associated with brain mineralization. This review contains 26 highly rendered figures, 15 tables, and 71 references. Key words: Inborn errors of metabolism, organic acidemia, cobalamin disorders, aminoacidopathy, lysosomal disorders