Ketone Body Therapy with D/L-β-hydroxybutyric Acid Solution in Severe MADD

Objectives: Multiple acyl-CoA dehydrogenase deficiency (MADD) is a severe inborn disorder of mitochondrial fatty acid oxidation. The only treatment option for MADD is the use of exogenous ketone bodies, like sodium beta-hydroxybutyrate (Na beta HB). However, the use of ketone body salts leads to a high intake of accompanying minerals, which can lead to additional side effects. The use of mineral-free formulations could improve tolerability. Methods: In this report, the use of a beta HB acid (beta HBA) in a patient with MADD is described. The production of D/L-beta HBA was carried out using ion exchange chromatography (IEX) and using a precipitation method. During two inpatient treatment intervals, the tolerability as well as clinical and metabolic effects were monitored. D-beta HB in serum, blood gas analysis, and standard blood measurements (like minerals) were used as control parameters. Results: Production of D/L-beta HBA using the precipitation method was more effective than using IEX. The tube feed solution used had a minimum pH of 3.5. Capillary D-beta HB measurements were between 0.1 and 0.4 mmol/L and venous were at 0.1 mmol/L or below. Minerals and serum pH were within the normal range. During application of D/L-beta HBA, gastrointestinal discomfort occurred and no clinical improvement was observed. Conclusions: The use of D/L-beta HBA in the therapy of severe MADD could be a good addition to the use of classical ketone body salts. The observed gastrointestinal side effects were of a mild nature and could not be specifically attributed to the D/L-beta HBA treatment. In short-term application, no clinical benefit and no substantial increase of D-beta HB in serum were noted. No tendency towards acidosis or alkalosis was observed during the entire period of treatment.