Ethylmalonic/adipic aciduria: effects of oral medium-chain triglycerides, carnitine, and glycine on urinary excretion of organic acids, acylcarnitines, and acylglycines.
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 mg/kg/d) 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 chromatography/mass spectrometry, and radioisotopic exchange HPLC, respectively. The excretion of each group of metabolites was calculated as the mean percentage of total output (mumol/24 h) during the four phases of the protocol (organic acids/acylglycines/acylcarnitines = 100.0%): 1) regular diet (3 d); 88.1/10.8/1.1; 2) medium-chain triglyceride supplementation (4); 82.5/15.6/1.9; 3) medium-chain triglycerides plus carnitine (5); 79.2/8.2/12.6; 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.
Rinaldo
P
P
Department of Genetics, Yale University, New Haven, Connecticut 06510.
Welch
R D
RD
Previs
S F
SF
Schmidt-Sommerfeld
E
E
Gargus
J J
JJ
O'Shea
J J
JJ
Zinn
A B
AB
D000215:Acylation; D000272:Adipates / Q000652:urine*; D000284:Administration, Oral; D002331:Carnitine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000652:urine; D002648:Child; D044927:Electron-Transferring Flavoproteins; D044943:Fatty Acid Desaturases / Q000172:deficiency; D005260:Female; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000652:urine; D006801:Humans; D007506:Iron-Sulfur Proteins; D008314:Malonates / Q000652:urine*; D008661:Metabolism, Inborn Errors / Q000188:drug therapy / Q000652:urine*; D009097:Multienzyme Complexes / Q000172:deficiency; D000587:Oxidoreductases Acting on CH-NH Group Donors; D014280:Triglycerides / Q000008:administration & dosage
D000272:Adipates; D044927:Electron-Transferring Flavoproteins; D007506:Iron-Sulfur Proteins; D008314:Malonates; D009097:Multienzyme Complexes; D014280:Triglycerides; C038080:ethylmalonic acid; C029900:adipic acid; D044943:Fatty Acid Desaturases; D000587:Oxidoreductases Acting on CH-NH Group Donors; C023120:electron-transferring-flavoprotein dehydrogenase; D002331:Carnitine; D005998:Glycine