Lactic acidosis congenital

Patients with complex I deficiency may also present with severe congenital lactic acidosis, hypotonia, weakness, cardiomyopathy, and cardiorespiratory failure caus-... 

Mutations in one nuclear gene (ATP12), encoding an ATPase assembly protein, have been associated with complex V deficiency in an infant with congenital lactic acidosis and a rapidly fatal disorder affecting brain, liver, heart, and muscle [19]. 

Most common biologic cause of congenital lactic acidosis... 

Figure 17.4 The electron transport chain of mitochondria. Triangles indicate sites of inhibition by various compounds. Cyt, cytochrome ETF, electron transfer flavoprotein. (Reproduced with permission from Moreadith RW, Batshaw ML, Ohnishi T, Kerr D, Knox B, Jackson D, Hruben R, Olson J, Reynafarje B, Lehninger AL. Deficiency of the iron-sulfur clusters of mitochondrial reduced nicotinamide-adenine dinucleotide-ubiquinone oxidoreductase (complex I) in an infant with congenital lactic acidosis J Clin Invest 74 685-697, 1984.)...

Biotin is a cofactor of various carboxylases, but its effectiveness in pyruvate carboxylase deficiency is unproven. However, it has been used effectively in cases of biotinidase deficiency, a vary rare cause of congenital lactic acidosis. 

Kerr DS Treatment of congenital lactic acidosis review. Inlem Pediatr 10 75-81,1995. 

Stacpoole PW, Barnes CL, Hurbanis MD, et al. Treatment of congenital lactic acidosis with dichloroacetate a review. Arch Dis Child 77 535-541,1997. 

A. Alpha-ketoglutarate dehydrogenase deficiency presenting as congenital lactic acidosis. J. Pediatr. 1992 121 255-258. 

Bonnefont JP, Chretien D, Rustin P, Robinson B, Vassault A, Aupetit J, Charpentier C, Rabier D, Saudubray JM, Munnich A. Alpha-ketoglutarate dehydrogenase deficiency presenting as congenital lactic acidosis. J. Pediatr. 1992 121 255-258. 

Congenital lactic acidosis Lactic, pyruvic, 2-oxoglutaric... 

V y of pyruvate, fatty acids, and other fuels. In many cases, the inhibition of mitochondrial electron transport results in higher than normal levels of lactate and pyruvate in the blood and an increased lactate/pyruvate ratio. NADH oxidation requires the completed transfer of electrons from NADH to O2, and a defect anywhere along the chain will result in the accumulation of NADH and decrease of NAD+. The increase in NADH/NAD inhibits pyruvate dehydrogenase and causes the accumulation of pyruvate. It also increases the conversion of pyruvate to lactate, and elevated levels of lactate appear in the blood. A large number of genetic defects of the proteins in respiratory chain complexes have, therefore, been classified together as "congenital lactic acidosis."... 

Gas Chromatographic and Mass Spectro-metric Studies on Urinary Organic Acids in a Patient with Congenital Lactic Acidosis Due to Pyruvate Decarboxylase Deficiency Clin. Chim. Acta 77(2) 117-124 (1977) CA 87 51177s... 

Investigation of the redox status in plasma on the basis of the molar L/P and B/A ratios in vivo can help to discriminate between several causes of congenital lactic acidosis. An intravenous glucose loading test (GTT 2 g/kg b.w.) might be advantageous to get more information about the redox status. An increased L/P ratio and a normal or decreased B/A ratio would be suggestive for a defect in the citric acid cycle. 

A randomized controlled trial in children with congenital lactic acidosis found that while DCA was well tolerated, it was ineffective in improving clinical outcomes. A separate trial of DCA in children with MELAS (a syndrome of inadequate mitochondrial function, leading to lactic acidosis) was halted early, as all 15 of the children receiving DCA experienced significant nerve toxicity without any evidence of benefit from the medication. A randomized controlled trial of DCA in adults with lactic acidosis found that while DCA lowered blood lactate levels, it had no clinical benefit and did not improve hemodynamics or survival. 

Chalmers, R.A., Lawson, A.M. and Borud, O. (1977c), Gas chromatographic and mass spectrometric studies on urinary organic acids in a patient with congenital lactic acidosis due to pyruvate decarboxylase deficiency. Clin. Chim. Acta, 11 j 117. 

Lindstedt, S., Norberg, K., Steen, G. and Wahl, E. (1976), Structure of some aliphatic dicarboxylic acids found in urine of an infant with congenital lactic acidosis. Clin. Chem., 22,1330. 

Borg, L., Lindstedt, S., Steen, G. and Hjalmarson, O. (1972), Aliphatic C6-C14 dicarboxylic acids in urine from an infant with fatal congenital lactic acidosis. Clin. Chim. Acta, 41,363. 

Blass, J.P., Schulman, J.D., Young, D.S. and Horn, E. (1972), An inherited defect affecting the tricarboxylic acid cycle in a patient with congenital lactic acidosis. J. Clin. Invest., 51,1845. 

Farrell, D.F., Clark, A.F., Scott, C.R. and Wennberg, R.P. (1975), Absence of pyruvate decarboxylase activity in man a cause of congenital lactic acidosis. Science, 187,1082. 

Robinson, B.H. and Sherwood, W.G. (1975), P5n uvate dehydrogenase phosphatase deficiency - cause of congenital chronic lactic acidosis in infancy. Pediatr. Res., 9,935. 

Saudubray, J.M., Marsac, C., Charpentier, C., Cathelineu, L., Besson Leaud, M. and Leroux, J.P. (1976), Neonatal congenital lactic acidosis with pyruvate carboxylase deficiency in two siblings. Acta Paediatr. Scand., 65,717. 

Scharer, K. (1972), Congenital lactic acidosis. In The Organic Acidurias, (eds. J. Stem and C. Toothill), Churchill Livingstone, Edinburgh and London, p. 46. 

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