212 R. G. WESTALL 
The “overflow” aminoacidurias 
Phenylketonuria. In 1934, FOLLING® observed that there was an excessive excretion 
of phenylpyruvic acid in the urine of certain mentally defective patients. Further 
studies established that the disease was hereditary and that the defect seemed to 
be handed on as a typical Mendelian recessive character. It is now known that phenyl- 
pyruvic acid is not the only metabolite which is excreted excessively in these cases; 
phenylacetic acid, phenyllactic acid and phenylacetylglutamine are also impli- 
THR 
Guu 

+ 
Fig. 13. A paper chromatogram of the urine of a child with maple-syrup-urine disease. 
cated®*, 86, 67, Phenylalanine, the immediate precursor of phenylpyruvic acid, is also 
present in the urine in high concentration (Fig. 11) and, indeed, is also found in ex- 
cessive amount in the blood plasma (Fig. 12) and the C.S.F.®~!. The site of the meta- 
bolic lesion in this disease is at the conversion of phenylalanine to tyrosine and these 
patients lack the phenylalanine hydroxylating enzyme which catalyses this step” *. 
Hence in this disease, where one of the major pathways of phenylalanine metabolism 
is blocked, this amino acid tends to accumulate in the body tissues and fluids. Some 
of the phenylalanine is deaminated to form phenylpyruvic acid and thence, by further 
References p. 217/219 
