2-Methyl-3-hydroxybutyric aciduria

Figure 20.20 Pathways of branched-chain amino acid metabolism. A, B, C, D, E, and F indicate defects in valinemia, maple syrup urine disease, isovaleric acidemia, /3-hydroxyisovaleric aciduria, a-methyl-j3-hydroxybutyric aciduria, and methylmalonic aciduria, respectively.

Diagnosis may be made using gas chromatography alone (Gompertz et al, 1974), and this may be illustrated by reference to methylmalonic aciduria. Fig. 9.3 shows the chromatogram of amniotic fluid containing 9 tg of methyl-malonate ml as its methyl ester, obtained by ether extraction. Because of the possible confusion of methylmalonate with 3-hydroxybutyrate, a normal amniotic fluid constituent (Section 8.1), or 2-methyl-3-hydroxybutyrate, depending on the GC column used, these authors advised the use of mass... 

Fig. 10.1 Metabolites in the urine of an untreated patient with branched-chain keto aciduria (maple syrup urine disease). Extracted using ethyl acetate and separated as their trimethylsilyl-oxime derivatives on a 25 m SE-30 capillary column, using temperature programming from 80°C to 110°C at 0.5°C min and an injection split ratio 1 12 at a temperature of 250°C. The peaks marked R are due to solvent and reagents. Peak identifications are 1, lactic 2, 2-hydroxyisobutyric 3, 2-hydroxybutyric 4, pyruvic 5, 3-hydroxybutyric 6, 2-hydroxyisovaleric 7, 2-oxobutyric 8, 2-methyl-3-hydroxy-isovaleric 10, a and b, 2-oxoisovaleric 11, acetoacetic 12, 2-hydroxyisocaproic 13, 2-hydroxy-3-methyl- -valeric 14, 2-oxo-3-methyl-/i-valeric (14a L- 14b D-) 15, 2-oxoisocaproic acids. The internal standard was malonic acid. (Redrawn with modifications from Jellum etal., 1976)...

Fig. 10.3 Chromatogram of organic acids extracted from the urine of an untreated patient with branched-chain keto aciduria (maple syrup urine disease), extracted and separated as described in the legend to Fig. 10.2. The chromatogram illustrates the overlapping peaks in the regions occupied by 3-hydroxybutyric, 2-hydroxyisovaleric and 2-oxoisovaleric acids (peak 1) and 2-oxo-3-methyl-valeric, 2-hydroxyisocaprioic and 2-oxoisocaproic acids (peak 2) and phosphate (peak 3). Other peaks of interest are (4) citric, (5) 4-hydroxyphenyl-lactic, (6) 4-hydroxyphenylpyruvic, (7) n-tetracosane (standard) and (8) -hexacosane (standard). (Compare with Fig. 10.4.)...

Gompertz, D., Saudubray, J.M., Charpentier, C., Bartlett, K., Goodey, P.A. and Draffan, G.H. (1974), A defect in L-isoleucine metabolism associated with a-methyl-/S-hydroxybutyric and a-methylacetoacetic aciduria Quantitative in vivo and in vitro studies. Clin. Chim. Acta, 57,269. 

Halvorsen, S., Stokke, O. and Jellum, E. (1979), A varient form of 2-methyl-3-hydroxybutyric and 2-methylacetoacetic aciduria. Acta. Paediatr. Scand., 68,123. 

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