Hyperammonemia ornithine transcarbamylase, deficiency

It may be concluded that in many cases of an ornithine transcarbamylase deficiency, there is an associated carbamyl phosphate deficiency, usually of moderate degree. It is because of this that it has even been suggested (E2) that hyperammonemia might not be due solely to ornithine transcarbamylase deficiency. This view cannot be correct in at least two cases where the carbamyl phosphate synthetase was within the normal, albeit low normal, range. 

Levin et al. has shown that whereas the ornithine transcarbamylase deficiency is severe and critical in most cases of hyperammonemia, in one child, a boy, the enzyme activity was reduced to a lesser extent (L6). Further investigations showed that other differences between the enzyme in this child and in others affected, existed. Thus the affinities of the enzyme for both carbamyl phosphate and ornithine were markedly different in this child from the others. On the basis of these findings they suggested that this constituted a distinct genetic variant, which could explain its occurrence in a male infant whereas all other reported cases of hyperammonemia were in females. 

The specific syndrome arising from a severe deficiency of ornithine transcarbamylase has been termed hyperammonemia (L2) (Fig. 9). Next to argininosuccinic aciduria, this in the most frequently reported of the enzymatic disturbances of the urea cycle eleven proved examples... 

Although ornithine transcarbamylase is fairly widely distributed in the tissues, only the enzyme levels in the liver in hyperammonemia have been adequately reported (Table 7), except that in one affected infant and the mother of two others, the small intestinal mucosa has also been examined (L8). In a series of 8 children, 7 females and 1 male, the liver ornithine transcarbamylase activity was 10% or less of the mean normal value, with the exception of the male, in whom the residual enzyme activity was as much as 25% of the mean normal. In 6 cases in whom the activity was also determined at pH 8.3, the reduction was much more variable, the activity varying from 11% to 40% of the mean normal an exception is the case mentioned previously, in whom the activity was actually within the normal range at that pH although slightly lower than the mean normal. These results together with the patient reported by Hopkins et al. (H5) proved conclusively that hyperammonemia is due to a gross deficiency of ornithine transcarbamylase activity. One other case, reported by Corbeel et al. (C12, C13), showed a somewhat... 

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