LAUSR

OBJECTIVES Multiple acyl-CoA dehydrogenase deficiency (MADD) is the most severe disorder of mitochondrial fatty acid β-oxidation. Treatment of this disorder is difficult because the functional loss of the electron transfer flavoprotein makes energy supply from fatty acids impossible. Acetyl-CoA, provided by exogenous ketone bodies such as NaßHB, is the only treatment option in severe cases. Short-term therapy attempts have shown positive results. To our knowledge, no reports exist concerning long-term application of ketone body salts in patients with severe MADD. METHODS This case report is a detailed retrospective metabolic analysis of a boy with severe MADD. Treatment with sodium β-hydroxybutyrate (NaβHB) started 8 d after birth using gradually increasing doses. In the initial phase, metabolic and acid-base parameters were checked multiple times a day. After 8 y of standardized therapy with 16 g NaβHB, substitution with calcium β-hydroxybutyrate (CaβHB) was attempted. In addition to the β-hydroxybutyrate (βHB) supplementation, continuous adjustments were made to the child's nutrition to provide necessary nutrients. RESULTS Treatment with βHB salts leads to adverse effects like gastrointestinal discomfort and alkalosis. Measured concentrations of βHB were predominantly at 0.1 mmol/L or below detectable concentration. Nutritional therapy based on amino acid and acylcarnitine profiles is a necessary part of the therapy in MADD. CONCLUSIONS Therapy with NaβHB is lifesaving in cases of severe MADD but can have significant adverse effects. Supplementation with CaβHB led to gastrointestinal discomfort and had no additional positive clinical effect. The determined tolerable dose of βHB salt for long-term therapy was not high enough for a notable increase of βHB concentrations in blood.