Branched chain ketoaciduria

Patients snffering from metabolic disorders such as phenylketonuria (PKU), branched-chain ketoaciduria (maple syrup urine disease, MSUD), nrea and ammonia disorders or glycogen storage disease reqnire formulations manufactured specifically for each disease (Elsas Acosta, 2006). (Appendix 15.1). 

Maple syrup urine disease (branched-chain ketoaciduria) <0.4 Isoleucine, leucine, and valine degradation Branched-chain a-keto acid dehydrogenase complex Vomiting convulsions mental retardation early death... 

Although alcaptonuria is a relatively harmless condition, such is not the case with other errors in amino acid metabolism. In maple syrup urine disease, the oxidative decarboxylation of a-ketoacids derived from valine, isoleucine, and leucine is blocked because the branched-chain dehydrogenase is missing or defective. Hence, the levels of these a-ketoacids and the branched-chain amino acids that give rise to them are markedly elevated in both blood and urine. Indeed, the urine of patients has the odor of maple syrup—hence the name of the disease (also called branched-chain ketoaciduria). Maple syrup urine disease usually leads to mental and physical retardation unless the patient is placed on a diet low in valine. 

Branched-chain ketoaciduria (commonly known as Maple Syrup Urine Disease MSUD) is another ailment that may be caused by thiamine deficiency. In MSUD, the oxidative decarboxylation of alpha-keto acids derived from, i.e. valine, isoleucine, and leucine, is blocked due to an inadequate supply of the coenzyme thiamine pyrophosphate (TPP). Clinical symptoms of MSUD include mental and physical retardation. Describe briefly the structure of Riboflavin (Vitamin B-2) and its biochemical role. 

Unlike other disease entities, excejit for canine cystinuria, no other nonhuman inherited amino acid disorders have been uncovered. In place of animal studies, increasing emphasis is being placed on the use of cultured explants of tissues removed from patients with hereditary metabolic disease. Cultured explants of skin, leukocytes, and erythrocytes have been used to study the metabolism of such disorders as citrullinemia, branch-chain ketoaciduria, cystinosis, homocystinuria, and isovalericacidemia (S18). 

A similar success was observed for studies of branched-chain ketoaciduria in which the second stage of the catabolism of leucine, valine and isoleucine involves an oxidative decarboxylation. In patients with branched-chain ketoaciduria, this step is blocked for all three of these amino acids. The urine of these patients takes on the odour of maple syrup and hence this condition... 

Maple syrup urine disease (branched-chain ketoaciduria)... 

In maple syrup urine disease, also called branched chain ketoaciduria, the a-keto acids derived from leucine, isoleucine, and valine accumulate in large quantities in blood. Their presence in urine imparts a characteristic odor that gives the malady its name. All three a-keto acids accumulate because of a deficient branched chain a-keto acid dehydrogenase complex. (This enzymatic activity is responsible for the conversion of the a-keto acids to their acyl-CoA derivatives.) If left untreated, affected individuals experience vomiting, convulsions, severe brain damage, and mental retardation. They often die before 1 year of age. As with phenylketonuria, treatment consists of rigid dietary control. 

Figure 10. HPLC of amino and imino adds after post-column deiivatization with NBD-F (Ref. 162). Abbreviations a = Asp b=Thr C = Ser d = Glu e=Pro f = Gly g = Ala h = Cys i = Val j = Met k = Ile 1 = Leu m = Nle (internal standard) n = Tyr o = Phe p = Lys q = His r = Arg s = Om t = allo-l e. Profile A is of a standard mixture. Profile B is of amino adds eluted from a filter-paper blood spot of a patient with phenylketonuria, showing a normal profile but with an abnormally large phenylalanine peak. Profiles C and D are from patinets with branched chain ketoaciduria (maple syrup urine disease) and tyrosinaemia respectively. Reprinted with permission from Y. Watanabe and K. Imai, Anal. Chem., 55, 1786 (1983). Copyright (1983) American Chemical Sodety.

Intermittent Maple Syrup Urine Disease (Branched-Chain Ketoaciduria) Clin. Chim. Acta 40(1) 5-11 (1972) ... 

A similar success was observed for studies of branched chain ketoaciduria in which the second stage of the catabolism of leucine, valine and isoleucine involves an oxidative decarboxylation. In patients with branched chain ketoaciduria, this step is blocked for all three of these amino acids. The urine of these patients takes on the odour of maple syrup and hence this condition is also known as maple syrup urine disease. H NMR spectroscopy was used to study the urines of patients with such branched chain ketoaciduria. The spectra showed several abnormal metabolites including the amino acids leucine, isoleucine and valine and their corresponding transamination products. It was noted that 2-hydroxyisovalerate levels were very high in the urines of all the patients studied and that, as in other inborn errors of metabolism, the levels of urinary glycine were elevated. 

Pueschal, S.M., Baesnan, M.J., Shih, V.E. and Levy, H.L. (1979), Thiamine-responsive intermittent branched-chain ketoaciduria. J. Pediatr., 94,628. 

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