Long-term use of investigational β-Hydroxybutyrate salts in children with multiple acyl-CoA dehydrogenase or pyruvate dehydrogenase deficiency

• Published in: Molecular genetics and metabolism reports Vol. 40; p. 101104
• Main Authors: Morris, Andrew A.M., Cuenoud, Bernard, Delerive, Philippe, Mundy, Helen, Schwahn, Bernd C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2024; Elsevier
• Subjects: Case Report; Glutaric aciduria II; Ketone bodies; MADD; Pyruvate dehydrogenase deficiency; β-Hydroxybutyrate; D-βHB; NR; MRI; ETFDH; Ketone bodies; D,L-βHB; PICU; Na; PDH; KB; mg; Glutaric aciduria II; kg; 6-MWT; HIE; ETFQO; g; CK; FAD; VLCAD; IEM; NAD; β-Hydroxybutyrate; ETF; MADD; Pyruvate dehydrogenase deficiency; GRAS
• ISSN: 2214-4269; 2214-4269
• DOI: 10.1016/j.ymgmr.2024.101104

Several disorders of energy metabolism have been treated with exogenous ketone bodies. The benefit of this treatment is best documented in multiple acyl-CoA dehydrogenase deficiency (MADD) (MIM#231680). One might also expect ketone bodies to help in other disorders with impaired ketogenesis or in conditions that profit from a ketogenic diet. Here, we report the use of a novel preparation of dextro-β-hydroxybutyrate (D-βHB) salts in two cases of MADD and one case of pyruvate dehydrogenase (PDH) deficiency (MIM#312170). The two patients with MADD had previously been on a racemic mixture of D- and L‑sodium hydroxybutyrate. Patient #1 found D-βHB more palatable, and the change in formulation corrected hypernatraemia in patient #2. The patient with PDH deficiency was on a ketogenic diet but had not previously been given hydroxybutyrate. In this case, the addition of D-βHB improved ketosis. We conclude that NHS101 is a good candidate for further clinical studies in this group of diseases of inborn errors of metabolism.