Organic acidurias : proceedings of the ninth symposium of the Society for the Study of Inborn Errors of Metabolism / edited by J. Stern and C. Toothill.

  • Society for the Study of Inborn Errors of Metabolism.
Date:
1972
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Licence: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

Credit: Organic acidurias : proceedings of the ninth symposium of the Society for the Study of Inborn Errors of Metabolism / edited by J. Stern and C. Toothill. Source: Wellcome Collection.

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    52 ORGANIC ACIDURIAS metabolic studies were done, were, however, small and we measured the fasting levels. We did measure glucose levels also. They were within normal limits, and did not alter on thiamine therapy. We are happy to learn that you also have been able to observe a thiamine effect in a patient. Gompertz {London). Three defects in carboxylase activity have been described today involving propionyl CoA, ^S-methylcrotonyl CoA and pyruvate carboxylase. This is obviously a new group of inborn errors of metabolism. By analogy with the first two carboxylafe deficiencies have you tried the effect of biotin ? de Groat. We have, up to 100 mg per day, but without any effect on blood lactate and pyruvate levels, nor on the clinical condition of our patient. Polliti {Sheffield). Dr de Groot, you have suggested that one of the problems in your patients may be a deficiency of oxaloacetate, interfering in the utilisation of acetyl CoA in the Krebs tricarboxylic acid cycle. Perhaps this would be overcome by feeding aspartate. The extra ammonia available from the transamination would be useful in the correction of acidosis by the kidney and for the synthesis of alanine from pyruvate. de Grooi. This seems a useful suggestion, worthy of detailed study. Siokke {Oslo). Dr de Groot, pyruvate can easily be transaminated to alanine. Where the levels of lactate and pyruvate are high you would also expect the alanine level to be raised. Did you find this? de Grooi. Plasma alanine levels were indeed found to be high (0-72-0-97 mM). As illustrated in Fig. 1 the plasma alanine level with thiamine therapy was considerably lower (0-47 mM). Baerlocher {Zurich). Dr Schärer, I think we should not consider the enzyme pyruvate decarboxylase as the only cause of congenital lactic acidosis. Baker, 1970 {Lancet, 2, 13) reported a patient with fructose-1,6- diphosphatase deficiency who developed lactic acidaemia after a 20-hour fast, and hypoglycaemia after the ingestion of fructose or glycerol. In another report about a patient with the same enzyme defect hyperalanin- aemia is also mentioned. Recently we had the opportunity to study a 14-months old child who presented many of the symptoms of congenital lactic acidosis and who resembled the patient you showed in your film, including the flush*. Lactic acid levels were slightly raised (25-35 mg/100 ml) when the child was in good clinical conditions and on a normal diet. Fructose and glycerol loading produced hypoglycaemia and an increase in lactic acid level to a peak of 78 mg/100 ml. I suggest that your patient, too, may have a deficiency of fructose-l,6-diphosphatase. This defect should be excluded in patients with so-called congenital lactic acidosis. Schärer {Heidelberg). In our patient, hypoglycaemia was never observed. The replacement of sucrose in the diet by galactose did not improve the * See also Helv. paedicit Acta 26,489,1971.