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Long-term ketone body therapy of severe multiple acyl-CoA dehydrogenase deficiency: A case report

Fischer, Tobias, Och, Ulrike, Marquardt, Thorsten
Nutrition 2019 v.60 pp. 122-128
acetyl coenzyme A, acyl-CoA dehydrogenase, adverse effects, alkalosis, amino acids, boys, calcium, case studies, diet therapy, electron transfer, energy, enzyme deficiencies, fatty acids, flavoproteins, gastrointestinal system, ketone bodies, mitochondria, patients, salts, sodium
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.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.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.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.