Methylglutaconic aciduria

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. 

The true existence of this organic aciduria will depend on further case reports and detailed enzymology. However, some similarity in the presentation in both reports suggests the occurrence of a partial enzyme deficiency leading to a severe neurological disorder. The difference of these cases from those with 

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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. 

Methylc rotonylglycinur ia 3-Methylglutaconic aciduria, other types Biotinidase def 3-Oxothiolase def Methylmalonic acidemia Propionic acidemia L-2-Hydroxyglutaric aciduria Urea cycle disorders... 

Methylglutaconic aciduria, other types Mevalonic aciduria... 

Neutropenia 3 Methy Ic roto ny Iglyc inur i a 3 Methylglutaconic aciduria type 2 GSD IB... 

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). 

Costeff optic atrophy syndrome , type III 3-methylglutaconic aciduria 19ql3.2-ql33 258501... 

Primary defect not conclusively identified in Costeff optic atrophy syndrome and idiopathic 3-methylglutaconic aciduria. 

Fig. 6.1. The L-leucine degradative pathway. Reactions for which inherited metabolic disorders have not been conclusively identified include A, leucine-isoleucine aminotransferase and the majority of the 3-methylglutaconic acidurias (6.6-6.7). 6.1, Branched-chain a-ketoacid dehydrogenase (BCKD) complex, a reaction also occurring in the initial steps of L-isoleucine and L-valine degradation 6.2, isovaleryl-CoA dehydrogenase 6.3, 3-methylcrotonyl-CoA carboxylase 6.4, 3-methylglutaconyl-CoA hydra-tase 6.8, HMG-CoA lyase. Pathologic urinary metabolites used as specific markers in the differential diagnosis are presented in squares. Abbreviation Co A, coenzyme A...

Table 6 4. 3-Methylglutaconic aciduria> type I (3-methylglutaconyhCoA hydratase deficiency) ...

Table 6,6. Costeff optic atrophy syndrome (3-methylglutaconic aciduria, normal 3-methylglutaconyl-CoA hydratase ...

Methylglutaconic aciduria type I (3-methylglutaconyI-CoA hydratase deficiency) AF, cultured AFC II... 

Di Rocco, M., Caruso, U., Moroni, I. et al. (1999) 3-Methylglutaconic aciduria and hypermethioninaemia in a child with clinical and neuroradiological findings of Leigh disease. J. Inher. Metab. Dis., 22, 593-598. 

Holtmann, M.H., Galle, P.R., Stremmel, W. et al. (1998) 3-Methylglutaconic aciduria associated with hepatospelomegaly, macrocytic anaemia, fever episodes, recurrent infections, cervical lymphadenopathy and progressive decrease of physical performance. I. Inher. Metab. Dis., 21, 683-685. 

Urinary excretion of specific organic acids may suggest a mitochondrial defect. Cytochrome c oxidase defects and other respiratory chain defects have been demonstrated in some patients with ethylmalonic aciduria or 3-methylglutaconic aciduria. In certain cases intermediates of the citric acid cycle are also found in increased amounts in the urine. 

Greter, J., Hagberg, B., Steen, G. and Soderhjelm, U. (1978), 3-Methylglutaconic aciduria Report on a sibship with infantile progressive encephalopathy. Eur. J. Pediatr., 129,231. 

Wysocki, S.J., Wilkinson, S.P., Hahnel, R., Wong, C.Y.B. and Panegyres, P.K. (1976), 3-Hydroxy-3-methylglutaric aciduria, combined with 3-methylglutaconic aciduria. Clin. Chim. Acta, 70,399. 

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