Caveats when considering ketogenic diets for the treatment of pyruvate dehydrogenase complex deficiency

Objectives: We conducted a critical assessment of the use of diets high in fat and low in carbohydrate ("ketogenic") in the treatment of children with congenital lactic acidosis caused by mutations in the mitochondrial pyruva te dehydrogenase complex (PDC). Study design: The dietary composition of 18 subjects (11 from literature so urces and 7 previously unpublished cases) was analyzed for nutrient composi tion. The biochemical and clinical responses to a long-term ketogenic regim en were also evaluated. Results: There was lack of uniformity in the proportion of fat calories adm inistered and in the fatty acid composition of the diets. Ketogenic diets a re also generally high in protein, compared with the recommended dietary al lowance for age. Patient response to these regimens also varied considerabl y. Conclusions: Although ketogenic diets have become the standard of care For the treatment of PDC deficiency, data to support their use are based on a f ew uncontrolled case reports in which dietary composition varied widely. Fu rthermore, there are several theoretical reasons for concern about the long -term safety of high-fat, low-carbohydrate diets. A controlled, prospective evaluation of the risks and benefits of these regimens for patients with P DC deficiency is required to establish rational nutritional guidelines.