Efficacy and safety of D,L-3-hydroxybutyrate (D,L-3-HB) treatment in multiple acyl-CoA dehydrogenase deficiency

Abstract

Purpose: Multiple acyl-CoA dehydrogenase deficiency (MADD) is a life-threatening, ultrarare inborn error of metabolism. Case reports described successful D,L-3-hydroxybutyrate (D,L-3-HB) treatment in severely affected MADD patients, but systematic data on efficacy and safety is lacking. Methods: A systematic literature review and an international, retrospective cohort study on clinical presentation, D,L-3-HB treatment method, and outcome in MADD(-like) patients. Results: Our study summarizes 23 MADD(-like) patients, including 14 new cases. Median age at clinical onset was two months (interquartile range [IQR]: 8 months). Median age at starting D,L-3-HB was seven months (IQR: 4.5 years). D,L-3-HB doses ranged between 100 and 2600 mg/kg/day. Clinical improvement was reported in 16 patients (70%) for cardiomyopathy, leukodystrophy, liver symptoms, muscle symptoms, and/or respiratory failure. D,L-3-HB appeared not effective for neuropathy. Survival appeared longer upon D,L-3-HB compared with historical controls. Median time until first clinical improvement was one month, and ranged up to six months. Reported side effects included abdominal pain, constipation, dehydration, diarrhea, and vomiting/nausea. Median D,L-3-HB treatment duration was two years (IQR: 6 years). D,L-3-HB treatment was discontinued in 12 patients (52%). Conclusion: The strength of the current study is the international pooling of data demonstrating that D,L-3-HB treatment can be effective and safe in MADD(-like) patients.

Exogenous Ketone Supplements Improved Motor Performance in Preclinical Rodent Models

“…One limitation of these results is that we used racemic (R/S) βHB exclusively, because this was the most economical and commercially available product on the market for both experimental purposes and for consumer consumption at the time of the study. Racemic βHB has been used clinically in patients and consumers for years [ 79 ], and no serious adverse events from βHB supplement ingestion have been reported (CAERS open-FDA database), even with >1 million estimated servings consumed annually. Thus, our approach was to evaluate molecules, which may be economically feasible to translate to humans and would be accessible to end-users in the near future.…”

Recurrent Abdominal Pain, Vomiting, Velvet-Like Changes in the Small Intestine in a Patient with Multiple Acyl-CoA dehydrogenation Deficiency

“…MADD patients demonstrate multiorgan dysfunction especially in the case of catabolism 12 . D,L-3-hydroxybutyrate treatment is effective in improving clinical symptoms and survival in severely affected MADD cases 1 . Figures Figure 1 CT scan of the abdomen with contrast.…”

“…Multiple acyl-CoA dehydrogenation de ciency (MADD) is a ultrarare inborn error of metabolism in fatty acid oxidation and amino acid 1 . Patients with later-onset MADD develop progressive myopathy and heterogeneous symptoms of intermittent vomiting and hypoglycemia 2 .…”

Recurrent abdominal pain, vomiting, velvet-like changes in the small intestine in a patient with multiple acyl-CoA dehydrogenase deficiency: a case report

“…Therefore, we could not compare MADD patients demonstrate multiorgan dysfunction especially in the case of catabolism (17). D,L-3-hydroxybutyrate treatment is effective in improving clinical symptoms and survival in severely affected MADD cases (1).…”

“…Multiple acyl-CoA dehydrogenase deficiency (MADD) is a ultrarare inborn error of metabolism in fatty acid oxidation and amino acid (1). Patients with later-onset MADD develop progressive myopathy and heterogeneous symptoms of intermittent vomiting and hypoglycemia (2).…”