Glycinaemia ketotic

Three conditions show certain similarities and can be considered together ketotic glycinaemia [97], non-ketotic glycinaemia [98] and methylmalonic acidaemia [99]. In all three the concentration of glycine in the blood is from 12 to 70 mg per 100 ml (normal < 2 mg per 100 ml) and the concentration of glycine in the urine is from 4,000 to 8,000 mg... 

Both reactions are catalysed by serine hydroxymethyl-transferase (EC 2.1.2.1). In non-ketotic glycinaemia this enzyme is partly or completely inactive and glycine therefore accumulates [102]. 

In some patients with non-ketotic glycinaemia (including one patient shown to lack serine hydroxymethyltransferase) hypo-oxaluria has been found [98] though oxalic acid excretion is normal in others and, in some cases, hypo-oxaluria is intermittent. 

In ketotic glycinaemia, propionyl-CoA carboxylase is absent or inactive and, in consequence, propionic acid cannot be converted to D-methylmalonic acid [112]. Patients do not accumulate propionic acid, except in traces, but the concentration of glycine in the blood rises to 70 mg per 100 ml and that in the urine to 6,000 mg per g creatinine. No methylmalonic acid is detectable in blood or urine. 

In all three conditions the first signs commonly appear within 48 h of birth. The infant ceases to suck, becomes drowsy and may have convulsions. At this time marked ketosis appears in ketotic glycinaemia and methylmalonic acidaemia. Most affected infants go rapidly downhill and die within a few days or weeks of birth. In some cases the onset of symptoms is later, up to four months of age, and the disease runs a slower course with survival for several years. The survivors show mental and physical retardation (I.Q. seizures, E.E.G. abnormalities,... 

In non-ketotic glycinaemia, glycine and serine are toxic [115]. Treatment with a diet low in these two amino acids is effective in restoring the body chemistry to normal treated infants survive and the neurological signs decrease. 

In ketotic glycinaemia, glycine is without any toxic effect. Isoleucine, methionine and threonine, which yield propionic acid, are very toxic. Administration of one of these three amino acids rapidly causes ketosis, acidosis, lethargy and convulsions. Leucine and valine, which are not metabolized through propionic acid, are as toxic as isoleucine, threonine and methionine—all other amino acids are non-toxic [114]. The toxicity of leucine and valine is not understood. 

In methylmalonic acidaemia, leucine, valine, isoleucine, methionine and threonine are toxic and all other aimino acids (including glycine) are non-toxic, as is found in ketotic glycinaemia [99]. There is no explanation of the effect of leucine. 

Treatment of both ketotic glycinaemia and methylmalonic acidaemia is with a diet low in the five toxic amino acids. On this treatment children survive and thrive, though it is too soon for assessment of the effect on the G.N.S. 

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