ABSTRACT
A four-month-old child with non-ketotic hypoglycemia and rapidly progressive cirrhosis excreted in her urine large amounts of two unidentified organic acids in addition to a spectrum of saturated, unsaturated, and 3-hydroxy dicarboxylic acids in her urine. Gas chromatography/mass spectrometry of the trimethylsilyl derivative of one of the unknown compounds suggested the structure of 3-hydroxyoctanoic acid, which was confirmed by similar analysis of the authentic compound. The same organic acid was found in the child's plasma. The significance of 3-hydroxyoctanoic aciduria as a possible marker for a primary defect of 3-hydroxy fatty acid metabolism is discussed.
Subject(s)
Hydroxy Acids/urine , Hypoglycemia/urine , Female , Humans , InfantABSTRACT
Two infants have been studied with glutaric aciduria Type II. The clinical presentation was of an overwhelming illness very early in life; both infants died in the neonatal period. One had dysmorphic features. An acrid odor may be a clue to the diagnosis. Neonatal acidosis, hypoglycemia, and hyperammonemia are characteristic. Organic acid analysis revealed massive lactic aciduria and glutaric aciduria. A variety of other dicarboxylic acids and hydroxy acids and amino acids were found in elevated amounts in body fluids, along with elevated concentrations of butyric, isobutyric, 2-methylbutyric, and isovaleric acids. The pattern of metabolites accumulated is consistent with deficient activity of a number of acyl-CoA dehydrogenases.
Subject(s)
Glutarates/urine , Metabolism, Inborn Errors/urine , Amino Acids/blood , Dicarboxylic Acids/blood , Dicarboxylic Acids/urine , Genes, Recessive , Humans , Hydroxy Acids/blood , Hydroxy Acids/urine , Infant, Newborn , Male , Metabolism, Inborn Errors/blood , Metabolism, Inborn Errors/genetics , Renal Aminoacidurias/diagnosisABSTRACT
Twin male infant siblings who presented in Harrow, UK, with a Reye's-like syndrome associated with profound hypoglycaemia, vomiting, diarrhoea, coma and death in one child, with dicarboxylic aciduria, and similarities to Jamacian vomiting sickness (hypoglycin toxicity) have been shown to excrete large amounts of a previously unrecorded urinary organic acid. This has been identified as 5-hydroxyhexanoic acid by gas chromatography mass spectrometry using a synthesized standard. Concentrations observed were 340 and 330 mg g-1 creatinine in the two patients. The metabolic precursor of the urinary acid is suggested to be hex-4-enoic acid, a probable chemical toxin closely related to the active organic acid metabolite of hypoglycin. The possibility of omega - 1 oxidation of hexanoic acid to 5-hydroxyhexanoic acid in these and other patients with dicarbocylic aciduris is also discussed.
Subject(s)
Caproates/urine , Hypoglycemia/urine , Reye Syndrome/urine , Chemical Phenomena , Chemistry , Dicarboxylic Acids/urine , Female , Gas Chromatography-Mass Spectrometry/methods , Humans , Hydroxy Acids/urine , Hypoglycins/poisoning , Infant , Male , Plant Poisoning/urine , Pregnancy , TwinsSubject(s)
Caproates/urine , Hydroxy Acids/urine , Plant Poisoning/urine , Vomiting/urine , Diseases in Twins , Humans , Hypoglycins/poisoning , Male , Mass SpectrometryABSTRACT
We identified methylenecyclopropylacetic acid, a known metabolite of hypoglycin A, in the urine of two patients with Jamaican vomiting sickness. Excretion of unusual dicarboxylic acids such as 2-ethylmalonic, 2-methylsuccinic, glutaric, adipic and dicarboxylic acids with eight and 10 carbon chains were also detected in both patients. The amounts of these dicarboxylic acids were 70 to 1000 times higher than normal. These metabolites have also been identified in urine of hypoglycin-treated rats. This evidence links hypoglycin A to Jamaican vomiting sickness as its causative agent. Urinary excretion of short-chain fatty acids was also increased up to 300 times higher than normal. These results indicate that, despite their clinical and histologic similarities, the cause and biochemical mechanisms of Jamaican vomiting sickness differ distinctly from those of Reye's syndrome in which these abnormal urinary metabolites are not appreciably increased.
Subject(s)
Foodborne Diseases/metabolism , Fruit/poisoning , Vomiting/etiology , Animals , Child, Preschool , Cyclopropanes/metabolism , Diagnosis, Differential , Dicarboxylic Acids/urine , Fatty Acids, Volatile/blood , Fatty Acids, Volatile/urine , Female , Foodborne Diseases/etiology , Foodborne Diseases/urine , Gluconeogenesis , Humans , Hydroxy Acids/urine , Hypoglycemia/etiology , Jamaica , Rats , Reye Syndrome/diagnosis , Toxins, Biological/metabolism , Valerates/urineABSTRACT
We identified methylenecyclopropylacetic acid, a known metabolite of hypoglycin A, in the urine of two patients with Jamaican vomiting sickness. Excretion of unusual dicarboxylic acids such as 2-ethylmalonic, 2-methylsuccinic, glutaric, adipic and dicarboxylic acids with eight and 10 carbon chains were also detected in both patients. The amounts of these dicarboxylic acids were 70 to 1000 times higher than normal. These metabolities have also been identified in urine of hypoglycin-treated rats. This evidence links hypoglycin A to Jamaican vomiting sickness as its causative agent. Urinary excretion of short-chain fatty acids was also increased up to 300 times higher than normal. These results indicate that, despite their clinical and histological similarities, the cause and biochemical mechanisms of Jamaican vomiting sickness differ distinctly from those of Reye's syndrome in which these abnormal urinary metabolities are not appreciably increased.(AU)
Subject(s)
Humans , Child, Preschool , Rats , 21003 , Female , Plant Poisoning , Vomiting/etiology , Hypoglycins/poisoning , Cyclopropanes/metabolism , Diagnosis, Differential , Dicarboxylic Acids/urine , Fatty Acids, Volatile/blood , Fatty Acids, Volatile/urine , Foodborne Diseases/etiology , Foodborne Diseases/urine , Gluconeogenesis , Hydroxy Acids/urine , Hypoglycemia/etiology , Jamaica , Reye Syndrome/diagnosis , Toxins, Biological/metabolism , Valerates/urineABSTRACT
A patient is described in whom lactic acidosis of very severe degree was found to coincide with the presence of beta-methylcrotonic acid and rho-hydroxyphenyllactic acid in urine in large amounts, while beta-hydroxyisovaleric acid was found to be a relatively minor excretion product. Beta-methylcrotonic acid is demonstrated, for the first time, to be present in blood and CSF. These findings are discussed in relation to the patients previously reported to have beta-methylcrotonylglycinuria and raise the possibility that our patient's organic aciduria may be secondary to acquired disease rather than to an inborn error of metabolism.