An introduction to nutritional treatment in inborn errors of metabolism--different disorders, different approaches.

Treatment of metabolic disease aims to restore homeostasis, where possible. This can be achieved in a number of ways. For disorders of intermediary metabolism, treatment involves a thorough understanding of the disorder and the pathogenesis of the deleterious effects The various approaches indicated may involve substrate restriction, replacement of deficient products, removal of toxic metabolites or stimulation of residual enzymes. Newer therapies include enzyme replacement and gene therapy. Often, the cornerstone of treatment is dietary. Substrate restriction includes not only a diet low in the substrate indicated by the disorder, but also strict calorie support in times of illness to avoid catabolism. Useful levels of substrate restriction may require the use of supplements of "medical foods", for example amino acid mixtures. Provision of the deficient products is important in disorders affecting energy metabolism. To understand the problems involved in nutritional treatment it is helpful to consider examples of different types of disorders. In Maple syrup urine disease (MSUD), treatment with a very strict low-protein diet, supplemented by a branched-chain-free amino acid mixture is successful, but each intercurrent illness is hazardous, regimens for sick days vital, and strict lifelong treatment is needed. Treatment for phenylketonuria is similar in restricting a substrate but there is no tendency for systemic illness if the phenylalanine levels are too high. Disorders of the urea cycle are difficult dietary challenges because while a very low-protein diet is required, no specific amino acid needs to be avoided and there is a fine line between adequate protein intake and chronic catabolism. Fatty acid oxidation disorders affect energy production and can be detected by newborn screening using tandem mass spectrometry. For long-chain fatty acid disorders, long chain fats must largely be avoided and medium-chain fats must be substituted while strictly avoiding catabolism. Glycogen storage disorders require strict attention to providing carbohydrate, at all times including throughout the night. Many patients with inborn errors do not need any specific dietary therapy, (eg those with storage or neurodegenerative disorders), although all children benefit from an optimal diet, and sick children need this especially.