Treatment of cardiomyopathy and rhabdomyolysis in long-chain fat oxidation disorders using an anaplerotic odd-chain triglyceride - PubMed (original) (raw)

Case Reports

. 2002 Jul;110(2):259-69.

doi: 10.1172/JCI15311.

Affiliations

Case Reports

Treatment of cardiomyopathy and rhabdomyolysis in long-chain fat oxidation disorders using an anaplerotic odd-chain triglyceride

Charles R Roe et al. J Clin Invest. 2002 Jul.

Abstract

The current dietary treatment of long-chain fatty acid oxidation defects (high carbohydrate with medium-even-chain triglycerides and reduced amounts of long-chain fats) fails, in many cases, to prevent cardiomyopathy, rhabdomyolysis, and muscle weakness. We hypothesized that the apparent defect in energy production results from a depletion of the catalytic intermediates of the citric acid cycle via leakage through cell membranes (cataplerosis). We further hypothesized that replacing dietary medium-even-chain fatty acids (precursors of acetyl-CoA) by medium-odd-chain fatty acids (precursors of acetyl-CoA and anaplerotic propionyl-CoA) would restore energy production and improve cardiac and skeletal muscle function. We fed subjects with long-chain defects a controlled diet in which the fat component was switched from medium-even-chain triglycerides to triheptanoin. In three patients with very-long-chain acyl-CoA dehydrogenase deficiency, this treatment led rapidly to clinical improvement that included the permanent disappearance of chronic cardiomyopathy, rhabdomyolysis, and muscle weakness (for more than 2 years in one child), and of rhabdomyolysis and weakness in the others. There was no evidence of propionyl overload in these patients. The treatment has been well tolerated for up to 26 months and opens new avenues for the management of patients with mitochondrial fat oxidation disorders.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Production of [3-2H3]propionylcarnitine from C7, C9, and C15 by cultured fibroblasts from the VLCAD patient (black bars) and 50 control subjects (white bars, mean ± SE).

Figure 2

Figure 2

Urinary excretion of indices of propionyl overload (3-hydroxypropionate [3-OH-prop], propionylglycine [PropGlycine], methylcitrate [MeCitrate]) and pimelic in urine samples from 50 normal subjects (black bars), the VLCAD patients (gray bars; ten samples collected over 12 months), and ten patients with propionic acidemia (white bars).

Similar articles

Cited by

References

    1. Dimauro S, Dimauro PMM. Muscle carnitine palmitoyl transferase deficiency and myoglobinuria. Science. 1973;182:929–931. - PubMed
    1. Engel AG, Angelini C. Carnitine deficiency of human skeletal muscle associated with lipid storage myopathy: a new syndrome. Science. 1973;179:899–901. - PubMed
    1. Roe, C.R., and Ding, J.H. 2001. Mitochondrial fatty acid oxidation disorders. In The metabolic and molecular bases of inherited disease. 8th edition. C.R. Scriver, A.L. Beaudet, W.S. Sly, and D. Valle, editors. McGraw-Hill. New York, New York, USA. 2297–2326.
    1. Sweetman L. Newborn screening by tandem mass spectrometry: gaining experience. Clin Chem. 2001;47:1937–1938. - PubMed
    1. Saudubray JM, et al. Recognition and management of fatty acid oxidation defects: a series of 107 patients. J Inherit Metab Dis. 1999;22:488–502. - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources