BODY FLUIDS AND EFFECT OF HEREDITARY DISORDERS 215 
the culprit. The general opinion of those who have studied the biochemical aspects 
of the disease is that the metabolic block is at the stage of decarboxylation of the 
branched ketoacids where the chain is shortened by one C atom and the residue 
condenses with coenzyme A. This seems to be the most likely stage since later in the 
series of degradations the pathways of the branched acids diverge’. 

Fig. 16. A paper chromatogram of the urine of a typical f/-aminoisobutyric acid excretor. 
Argiminosuccimc aciduria. In 1958, ALLAN, CUSWORTH, DENT AND WILSON’ des- 
cribed a family in which two children, both mentally defective, excreted a large 
amount of an unknown amino acid-like substance in the urine (Fig. 15). It was, 
however, absent from the urine of the parents and of two other apparently normal 
siblings. The unknown substance could be detected in the plasma of the affected 
children and also in the C.S.F. where, curiously enough, the concentration was over 
twice as high as in the plasma. Later, the strange substance was isolated from the 
urinary source and characterized as argininosuccinic acid (ASA)8°, 
ASA was postulated to occur as an intermediate in the ornithine cycle*!. It has 
been found in plant tissue*? and in mould** but it had not been found previously to 
occur naturally in mammalian tissues or fluids. ASA can be synthesized in vitro by 
References p. 217/219 
