Disorders of L-leucine metabolism

3-methylcrotonylglycinuria (3-methylcrotonyl-CoA carboxylase deficiency, Also occurs in holocarboxylase synthetase or combined carboxylase deficiency) 

3-Hydroxy-3-methylglutaryl-CoA lyase deficiency, leading to 3-hydroxy-3-methylglutaric aciduria 

Concentrations of amino acids and sugars in blood were normal during ketotic attacks and remission, although concentrations of lactate and pyruvate were increased during keto acidosis. The frequency of the ketotic attacks (every 4-6 weeks) diminished as the patients grew older, but slight mental deficiency occurred in both patients (Tanaka, 1975). 

It is of interest that one of the cases of Sidbury et al (1967), who were described as having hexanoic and butanoic aciduria due to a proposed defect in short-chain fatty acid metabolism located at green acyl-CoA (butyryl-CoA) dehydrogenase, was subsequently shown to have isovaleric acidaemia (Ando et al, 1973) (Case 4, Family II of Sidbury etal, 1967). It is possible that the other three cases of Sidbury et al (1967) (Cases 1-3, Family I) also had isovaleric 

It has been suggested that heterozygotes for the disease may excrete increased concentrations of isovalerylglycine in their urine after a leucine load test (Guibaud et al., 1973) when compared to controls, in whom no excretion of this compound was observed. Serum leucine and isovaleric acid concentrations were not affected in similar tests carried out by others (Levy etai, 1973), but such a test with isovalerylglycine monitoring may be useful to demonstrate heterozygosity. 

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