Ethylmalonic/Adipic Aciduria: Effects of Oral Medium-Chain Triglycerides, Carnitine, and Glycine on Urinary Excretion of Organic Acids, Acylcarnitines, and Acylglycines

Abstract

ABSTRACT. A 9-y-old girl with ethylmalonic/adipic aciduria was hospitalized to determine the possible therapeutic efficacy of oral carnitine and glycine supplementation. To provoke a mild metabolic stress, her diet was supplemented with 440 mg/kg/d of medium-chain triglycerides. She was treated successively with carnitine (100 mg/kg/d) for 5 d, neither carnitine nor glycine for 2 d, and then glycine (250 mglkgld) for 6 d. Consecutive 12-h urine collections were obtained throughout the entire period. The urinary excretion of eight organic acids, four acylglycines, and four acylcarnitines, which accumulate as a result of a metabolic block of five mitochondrial acyl-CoA dehydrogenases, were quantitatively determined by capillary gas chromatography, stable isotope dilution gas chromatographylmass spectrometry, and radioisotopic exchange HPLC, respectively. The excretion of each group of metabolites was calculated as the mean percentage of total output (pmo1124 h) during the four phases of the protocol (organic acids/acylglycines/acylcarnitines = 100.0%): 1) regular diet (3 d); 88.1110.811.1; 2) medium-chain triglyceride supplementation (4); 82.5115.611.9; 3) medium-chain triglycerides plus carnitine (5); 79.218.2112.6; and 4) medium-chain triglycerides plus glycine (6); 81.0/18.7/0.3. Comparison between total and individual excretion of acylglycines and acylcarnitines indicates that oral glycine supplementation enhanced the conjugation and excretion of fatty acyl-CoA intermediates as efficiently as carnitine. We propose that oral glycine supplementation should be considered in the treatment of other inborn errors of metabolism associated with abnormal urinary excretion of acylglycines. (Pediatr Res 30: 216-221, 1991) Abbreviations AC, acylcarnitines AG, acylglycines BC, butyrylcarnitine BG, butyrylglycine ETF, electron transfer flavoprotein ETF-QO, ETF-ubiquinone oxidoreductase HC, hexanoylcarnitine HG, hexanoylglycine

Prenatal Diagnosis and Neonatal Monitoring of a Fetus with Glutaric Aciduria Type II Due to Electron Transfer Flavoprotein (β-Subunit) Deficiency

“…In contrast, in the mild form, the diagnosis may be more dificult because the organic aciduria is considerably less pronounced and often intermittent (1,(19)(20)(21). In this case, an increased excretion of hexanoylglycine in urine was detected by stable isotope dilution analysis immediately after birth and continued thereafter.…”

Relative Carnitine Deficiency in Autism

“…This feature sets the stage for the ''secondary carnitine deficiency'' syndromes, those that arise because of some metabolic block that has nothing to do with carnitine itself, but rather predisposes to high concentrations of acyl carnitines, and ultimate depletion of body carnitine stores through renal wasting (Famularo, Matricardi, Nucera, Santini, & DeSimone, 1997;Roe, 1997). Classical examples of inborn errors that produce a secondary carnitine deficiency include the family of diseases caused by mutations in the genes encoding the enzymes involved in fatty acid oxidation (Rinaldo et al, 1991;Roe & Ding, 2001), the family of organic acidemias caused by mutations in the genes encoding the enzymes involved in branched chain amino acid catabolism (Chalmers et al, 1984), and diseases produced by defects in the mitochondrial respiratory complexes (Brenningstall, 1990). Several drugs, most notably valproate, also cause a secondary carnitine deficiency (DeVivo et al, 1998;Farkas, Bock, Cseko, & Sandor, 1996).…”

Mammalian mitochondrial β-oxidation

“…Deficiency in either ETF or ETF : QO is termed glutaric aciduria type II [114] and was also known as multiple acyl-CoA dehydrogenation deficiency until recognition of the primary defect(s) by Christensen et al [115] and Frerman and Goodman [116]. The activities of all dehydrogenases served by ETF and ETF : QO are impaired [117].…”