Principles of inborn errors of metabolism: an exercise

Many inborn errors of intermediary metabolism present during periods of poor oral intake or intercurrent illness. Under these conditions, the body switches to a predominantly catabolic state, when glycogen, fat, and protein are mobilized as alternative energy sources. If a genetic defect already exists in any of these catabolic pathways, the problem is accentuated because the catabolic state demands a high flux of metabolite through these pathways. Therefore, a cardinal principle in the management of children who have IEM is to prevent them from lapsing into a catabolic state. This can be done through: 1) aggressive nutrition management to promote positive nitrogen balance and decrease accumulation of toxic metabolites, and 2) immunizations to minimize the possibility of viral or bacterial illness. When catabolism does occur, high-dose glucose infusion is a potent method for turning off the catabolic state. This simplistic view of the catabolic pathways neglects many details in each of the metabolic pathways and diseases cited in the article and questions. Nevertheless, it should provide a useful framework for explaining some of the clinical findings encountered in caring for this special group of patients. A partial list of more commonly encountered IEMs is contained in the Table. The different parts of the biochemical pathways discussed previously are combined into Figure 6. Hopefully, for some readers, the Figure also will lead to the affirmation that biochemistry is not so bad after all!