Ketonuria disease

As the name implies, the odor of urine in maple syrup urine disease (brancbed-chain ketonuria) suggests maple symp or burnt sugar. The biochemical defect involves the a-keto acid decarboxylase complex (reaction 2, Figure 30-19). Plasma and urinary levels of leucine, isoleucine, valine, a-keto acids, and a-hydroxy acids (reduced a-keto acids) are elevated. The mechanism of toxicity is unknown. Early diagnosis, especially prior to 1 week of age, employs enzymatic analysis. Prompt replacement of dietary protein by an amino acid mixture that lacks leucine, isoleucine, and valine averts brain damage and early mortality. 

The catabolism of leucine, valine, and isoleucine presents many analogies to fatty acid catabolism. Metabolic disorders of branched-chain amino acid catabolism include hypervalinemia, maple syrup urine disease, intermittent branched-chain ketonuria, isovaleric acidemia, and methylmalonic aciduria. 

Dl. Dancis, J., and Levitz, M., Maple syrup urine disease (branched chain ketonuria). In "The Metabolic Basis of Inherited Disease (J. B. Stanbury, J. B. Wyn-gaarden, and D. S. Fredrickson, eds.), 2nd Ed., pp. 353-365. McGraw-Hill, New York, 1966. 

In acute severe systemic intoxication abnormalities of routine clinical chemistry are usually present such as metabolic acidosis, increased anion gap, cytopenia, hypoglycemia, hyperammonemia (which can mask acidosis), lactic acidemia, elevations of triglycerides and free fatty acids, and ketosis. Testing for ketonuria is an especially simple and useful first line investigation. In most newborns as well as in older children with organic acid disorders, including some patients with fatty acid oxidation defects, there is pronounced ketonuria. Ketonuria is only rarely observed even in very sick newborns without metabolic disease. 

MAPLE SYRUP URINE DISEASE (BRANCHED-CHAIN KETONURIA) 235... 

Greer, M. and Williams, C.M. (1967), Diagnosis of branched-chain ketonuria (Maple syrup urine disease) by gas chromatography. Biochem. Med., 1,87. 

A further development in the description of the disease was reported by Robinson et al. (1979), who reported a patient, a female child of unrelated French-Canadian parents, who presented with metabolic acidosis, acetonuria and coma after a fever at 30 months of age. Her clinical condition deteriorated and she died with features of salicylism, including a serum salicylate of 20 mg dl A second child (female) born several years later to the same family subsequently presented at 1 year with fever, metabolic acidosis, vomiting and persistent tachypnoea. She had ketonuria, and an apparent serum salicylate of 11.2 mg dl despite having received no salicylates during the previous 6 days. GC-MS of urinary organic acids extracted using solvents revealed the presence of increased concentrations of lactate (510 mg per g of creatinine), 3-hydroxy-butyrate (2310 mg per g of creatinine), acetoacetate (2080 mg per g of creatinine), 2-methyl-3-hydroxybutyrate (480 mg per g of creatinine), 2-methylacetoacetate (572 mg per g of creatinine), 3-hydroxyisovalerate (470 mg per g of creatinine) and tiglylglycine (152 mg per g of creatinine). The apparent salicylate in serum was found to be due to acetoacetate. 

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