Hydroxy aciduria

Methyl 3-hydroxy butyric aciduria 2-Methyl 3-hydroxy butyryl-CoA dehydrogenase... 

Hydroxy 3-methyl glutaric aciduria 3-Hydroxy 3-methyl glutaryl-CoA lyase... 

Hydroxy butyric aciduria Succinic semialdehyde dehydrogenase... 

L-2-Hydroxy glutaric aciduria L-2-Hydroxy dehydrogenase (Duranin)... 

Fig. 5.1.1 Isoprenoid biosynthetic pathway. The enzyme mevalonate kinase (black solid bar) is deficient in patients affected with mevalonic aciduria and hyperimmunoglobulinemia D and periodic fever syndrome. -CoA -Coenzyme A, HMG-CoA 3-hydroxy-3-methyl-glutaryl-coenzyme A, -PP -pyrophosphate...

Individuals who are deficient in HMG-CoA lyase are unable to complete the metabolism of leucine. The increased urinary excretion of 3-hydroxy-3-methylglutaric acids is the primary biochemical criterion that distinguishes this particular enzymatic defect from other defects in enzymes of leucine catabolism that also result in metabolic acidosis and abnormal organic aciduria. There is also substantial urinary excretion of intermediates of leucine catabolism, such as 3-methylglutaconic acid, and their metabolites, including 3-hydroxy-isovaleric acid produced from isovaleric acid. 

The most Important use of body odors in disease diagnosis relates to the infant diseases involving errors in amino acid metabolism. Strong and unusual odors are manifest in the breath, sweat, and urine of these individuals. Table II summarizes several known acidurias, the amino acids that are not properly metabolized, and the odors associated with the compounds which accumulate and can be detected in the urine ( ). In the case of the Maple Syrup Urine and Oasthouse syndrome, the keto- and hydroxy- acids which have been identified may not be responsible for the observed maple and celery/yeast odors (.9). Alternatively, these odors could be the result of conversion of 2-keto-butyrlc acid to methyl-ethyl-tetronlc acid (Slusser s lactone) which is used as an extender in maple and celery flavors and has a maple syrup-like odor (R. Soukup, personal communication). With these acidurias it is imperative that an immediate diagnosis is made, since corrective diet can prevent the brain damage that results from these diseases. This is readily done on an olfactory basis which can subsequently be supported by gas chromatographic... 

Isovaleric acidemia Glutaric acidemia type II 3-Hydroxy-3-methylglutaric aciduria... 

Sweaty feet Isovaleric acid Isovaleric acidemia 3-Hydroxy-3-methylglutaric aciduria MAD... 

Methy Icroto nylglydnur ia 3-Methylglutaconic aciduria, other types 3-Hydroxy-3 methylglutanyl CoA synthase def. 3-Hydroxy-3-methylglutanyl-CoA lyase def. HIHA-syndrome (hyper insulin ism + hyperammonemia) Methylmalonic acidemia 2-Ketoglutarate dehydrogenase complex def. 

Cholesterol 4 3-Methylglutaconic acidurai, other types Mevalonic aciduria Abetalipoproteinemia Hypobetalipoproteinemia 3 -Hydroxy-A -C27-steroid dehydrogenase (3/ -HSDH) def 3reductase def (5 -reductase def) Smith-Lemli-Opilz syndrome Barth syndrome Glucosyltransferase I def CDG-Ic... 

Methylglutaric acid n.d n d. n.d n.d. n.d. 3-Methyl-glutaconic acidurias (6) 3-hydroxy-3-methylglutaric aciduria (6)... 

The inborn errors of L-leucine catabolism present biochemically with branched-chain amino and/or organic aciduria [1]. These disorders include maple syrup disease (MSD branched-chain a-ketoacid dehydrogenase (BCKD) deficiency), isovaleric acidemia (isovaleryl-coenzyme A (CoA) dehydrogenase deficiency), isolated 3-methylcrotonyl-CoA carboxylase deficiency, the 3-methylglutaconic acidurias (3-methylglutaconyl-CoA hydratase deficiency, Barth syndrome, and other disorders in which the primary defect has not been demonstrated), and 3-hydroxy-3-methylglutaric aciduria (3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) lyase deficiency). 

Chen E, Nyhan WL, Jakobs C, Greco CM, Barkovich AJ, Cox VA, et al. L-2-Hydroxy-glutaric aciduria neuropathological correlations and first report of severe neurode-generative disease and neonatal death. / Inher Metab Dis 1996 19 335-343... 

Approximately thirteen cases of 2-aminoadipic aciduria have been reported in the literature. Nine of the reported patients excreted in addition more or less significant amounts of 2-oxoadipic acid, some also 2-hydroxy-adipic acid and variable amounts of glutaric acid. The latter results obviously from spontaneous decarboxylation of 2-oxoadipic acid. 

The final part deals with the organic acidurias themselves. In addition to their common chemical and biochemical features of the accumulation of water-soluble, ninhydrin-negative, organic carboxylic, hydroxy, 0x0 and other acids. 

Hydroxy-3-methylglutaric aciduria 3-Methylglutaconic, 3-hydroxy-3-methylglutaric, 3-hydroxyiso-valeric and 3-methylglutaric acids 3-Hydroxy-3-methylglutaryl-CoA lyase (EC 4.1.3.4) 10.3.4... 

The majority of patients described in the literature have the classical form of the disease, and may be detected by their abnormal amino acidaemia and amino aciduria. The oxo acids may be detected by dinitrophenylhydrazine testing and characterized by thin-layer chromatography (Seakins etal.y 1976). The use of gas-liquid chromatography and mass spectrometry is greatly preferable, however, since the associated hydroxy acids and other metabolites may be studied simultaneously. The excretion of these metabolites in the urine is rapid, and blood concentrations are comparatively low. The concentration of 0X0 acids is also increased in cerebrospinal fluid. 

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)...

There have been two reports concerning three patients with 3-methylglutaconic aciduria with proposed deficiency of 3-methylglutaconyl-CoA hydratase, which normally hydrates the unsaturated acid to 3-hydroxy-3-methylglutaryl-CoA. 

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