Congenital abnormalities of amino acid transport in renal tubules.

ADDRESS: 219 Bryant Street, Buffalo 22, New York. V ARLETLES of syndromes have been described in which an abnormal amount of organic acid appears in the urine. In many of those syndromes which have been carefully studied, amino acids appear to constitute the major portion of organic acids. This probably is the result of the development of adequate methodology for the determination of amino acids. Nevertheless, the author proposes classifying these diseases as organic acidurias, since it is his belief that there are organic acids, other than amino acid, present in the urine of these patients. Although the central theme of the Symposium of which this paper is a part is genetic defects, in the classification which is to be presented for consideration, some syndromes are included which are not genetic in origin. This is done for the purpose of completeness and to suggest the relationships between the syndromes with a genetic background and those in which the organic aciduria results from some nongenetically controlled aberrations. These syndromes may be roughly divided into two groups : Those in which the concentration of amino acids in the blood is elevated and those in which it is normal. The problem of classification of these syndromes has recently been reviewed in detail.1’ 2 In the group of syndromes with normal concentrations in the blood, further subdivision is necessary into four apparently different groups. In Table I are listed the diseases falling into these various categories. Among the diseases characterized by elevated concentration of organic acids in the blood, one may observe that only phenylpyruvic oligophrenia represents a congenital anomaly. This has been discussed in detail in this Symposium in a lucid exposition presented by Dr. Meister. The other syndromes in this classification are clearly beyond the scope of a symposium on a genetically determined illness. It is also clear that none of the syndromes resulting from renal intoxication (group ha, Table I) are within the scope of this Symposium since in no instance do these represent genetically controlled disease. The diseases in group lib include a host of syndromes which are of great interest to both geneticists and biochemists. These all appear to be genetically controlled in that, in all eases, there are many more examples of the disease within families than among the general population. Cystine-lysinuria is a syndrome eharacterized by the appearance in the urine of abnormally large amounts of cystine, bysine and ornithine. On the basis of experiments in which cystine and cysteine were fed to both normal subjects and those with cystinuria, it was proposed that this disease resulted from an aberration in the metabolism of 4 It is clear, however, as a result of recent observations, that this interpretation is incorrect.5 The abnormality is entirely renal in origin, and the finding of organic acids in the urine results from impaired tubular reabsorption of tile involved amino acids. In fact, the clearance of cystine is equal to the gbomerular filtration rate.6 H-syndrome or Hartnup syndrome is a distinct entity recently described by Dent and associates.7 It is characterized by the appearance in the urine of a variety of amino acids, but what is of particular interest to the pediatrician and geneticist is