Dataset Information

Ketone body therapy with D/L-β-hydroxybutyric acid solution in severe MADD.

ABSTRACT:

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 β-hydroxybutyrate (NaβHB). 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 βHB acid (βHBA) in a patient with MADD is described. The production of D/L-βHBA 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-βHB in serum, blood gas analysis, and standard blood measurements (like minerals) were used as control parameters.

Results

Production of D/L-βHBA using the precipitation method was more effective than using IEX. The tube feed solution used had a minimum pH of 3.5. Capillary D-βHB 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-βHBA, gastrointestinal discomfort occurred and no clinical improvement was observed.

Conclusions

The use of D/L-βHBA 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-βHBA treatment. In short-term application, no clinical benefit and no substantial increase of D-βHB in serum were noted. No tendency towards acidosis or alkalosis was observed during the entire period of treatment.

SUBMITTER: Fischer T

PROVIDER: S-EPMC6610240 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Publications

Ketone body therapy with D/L-β-hydroxybutyric acid solution in severe MADD.

Fischer Tobias T Elpers Christiane C Och Ulrike U Fobker Manfred M Marquardt Thorsten T

Molecular genetics and metabolism reports 20190628

<h4>Objectives</h4>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 β-hydroxybutyrate (NaβHB). 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.<h4>Methods</h4>In this report, the use of a βHB acid (βH ...[more]

PMID: 31312603

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Project description:Ketosis is common in high-yield dairy cows. It is a condition that is characterized by the accumulation of serum β-hydroxybutyric acid (BHBA). Both subclinical ketosis and clinical ketosis can compromise the reproductive performance and cause long-lasting negative effects on reproductive efficiency by affecting the proliferation of follicular and granulosa cells. However, the regulatory mechanisms involved in the development of follicular cells and granulosa cells in cows experiencing subclinical ketosis and clinical ketosis remain largely unknown. To investigate the effect of a ketosis-triggered increase in BHBA on bovine follicular granulosa cell development, we detected a significant reduction in the proliferation of granulosa cells (P < 0.05) in the BHBA-1.2 mM and BHBA-2.4 mM groups and a significant increase in the number of granulosa cells in the G1 phase of the cell cycle (P < 0.05). RNA-seq and trend analysis were used to identify differentially expressed genes by comparing three clusters: low-concentration response to 1.2 mM BHBA, high-concentration response to 2.4 mM BHBA, and the similar trend (up or down) response following BHBA concentration increased. GO and KEGG enrichment analyses were performed separately for each cluster. Analysis showed that two novel down-regulated genes (G0S2 and S100A6), which are associated with cell proliferation and cycle progression, were enriched in the low-concentration response to 1.2 mM BHBA. Another differentially expressed gene (PARP), which plays a role in the apoptotic pathway, was enriched in the high-concentration response to 2.4 mM BHBA. We also found that CYP27B1 and CYP17A1, which are associated with Ca2+ homeostasis and estrogen synthesis, were enriched in a similar trend response. In conclusion, we describe the dynamic transcription profiles of granulosa cells under different levels of β-hydroxybutyric stress and report key regulators that may underlie the detrimental effects on the development of follicles and granulosa cells, thus representing potential therapeutic targets to improve fertility in dairy cows with subclinical ketosis or clinical ketosis.

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Dataset Information

Ketone body therapy with D/L-β-hydroxybutyric acid solution in severe MADD.

Objectives

Methods

Results

Conclusions

Publications

Ketone body therapy with D/L-β-hydroxybutyric acid solution in severe MADD.

Similar Datasets

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