Downloaded from 242 CONFERENCEPROCEEDINGS '950 Green, H. N. (1943). Z,ancet, 245, 147. Green, H. PI;. & Stoner, H. B. (1947). Brit. 3. exp. Path. 28, 189. https://www.cambridge.org/core Green, H. N., Stoner, H. B. & Bielschowsky, M. (1949). J. Puth Ract. 61, 101. Green, H. K., Stoner, €1. B., Hiteley, H. J. & Elgin, D. (1949). Clin. Sci. 8, nos. I and 2. Grihble, M. de G., Peters, R. A. & Wakelin, H. W. (1947). J. Physinl. 106,36P. Grossman, C. M., Sappington, T. S., Burrows, B. A, Lavietes, P. H. & Peters, J. P. (1945). J. elin. Invest. 24, 523. Hallberg, L. (1950). I.uncet, 258, 351. Hirshfeld, J. W., Abbott, W. E., Pilling, M. A., Heller, C. G., Meyer, F., Williams, H. H., Richards, A. J. & Obi, R. (1945). Arch. Surg. 50, 194. HomburRer, F. (1948). Amer. J. Med. 5, 264. Howard, J. E., Parson, W., Stein, K. E., Eisenberg, €1. & Reidt,V. (1944). Johns Hopk. Hosp. Bull. 75,I 56. IP address: Howard, J. E., Winternitz, J., Parson, W., nigham, R. S. Jr. & Eisenberg, H. (1944). 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Sutg. 118. 215. Trueta, J., Barclay, A. E., Daniel, P., Franklin, K. J. & Prichard, M. M. L. (1946). Lancet, 251, 237. Varco, I<. L. (1946). Surgery, 19, 303. \'arco, 11. I,. (1947). Surf. Gynec. Obstet. 84, 611. Venning, H., de Vries, J. A. & Herbert, P. €1. (1947). Conference on Metabolic Aspects of Convalescence. E. https://www.cambridge.org/core/terms Trnnsactions of the Sixteenth Meeting, p. 146. Sew York: Josiah Macy Jr. Foundation. Werner, S. C. (1948). Am.J. Med. 5. 749. Werner, S. C., Habif, D. V., Randall, €I. T. & Lockwood, J. S. (1949). Ann. Surg. 130, 688. Whipple, G. H. & Madden, S. C. (1944). Medicine, 23, 215. White, A. & Dougherty, T. F. (1946). Ann. N.Y. Acad. Sci. 46, 859. Young, N. I:. (1948). Amer.J. Med. 5, 586. Diet and Inborn Errors of Metabolism By C. RIMINGTON,Department of Chemical Pathology, University College Hospital I . Medical School, University Street, London, W.C. https://doi.org/10.1079/BJN19500040 The title of my communication imposes upon me rather severe restrictions as to subject. Inborn errors are gene-controlled deviations from the normal and are almost Downloaded from VOl. 4 Therapeutic dietetics 243 certainly expressions of the absence from the affected organism of one or more enzymes. https://www.cambridge.org/core Those that have been encountered and studied in man and animals are, for the most part, relatively harmless, or at any rate non-lethal, aberrations and, being genetically controlled, are unlikely to be influenced by external conditions such as diet, except, possibly, in a quantitative manner. They may be physically striking as is, for example, albinism due to the absence of the enzyme system responsible for melanin production, and familial methaemoglobinaemia which imparts a slaty colour to the sufferer, or they may be of such a character as to go unnoticed for years. Alcaptonuria and cystinuria . IP address: may easily be overlooked in this way. Relatively few studies have been made of any effect exerted by diet upon metabolic errors except for those upon the metabolism of the aromatic amino-acids and, in 170.106.40.139 recent years, investigations upon cystinurics. I shall confine myself mainly, therefore, to a discussion of these conditions and of related, experimentally produced metabolic errors. Familial methaemoglobinaemia is also a condition of interest because the , on specific biochemical lesion has been identified and because it may be influenced by 02 Oct 2021 at 19:20:22 the administration of ascorbic acid or of methylene blue. The latter substance, it is true, must be regarded as a drug rather than as an article of diet, but it forms an effective substitute for the missing coenzyme in the red cell. Such conditions as diabetes and gout might possibly be regarded as metabolic errors and therefore suitable for inclusion in this review but I feel that they are in themselves , subject to the Cambridge Core terms of use, available at such big subjects and that so little is really known concerning their relation to diet that it would be more prudent to exclude them. I have also decided to exclude all errors induced in an organism by diet but not referable to an inborn genetic constitution. KO account will thus be taken of the effects of carcinogens or of chemically induced mutations, of vitamin deficiencies or of antivitamins like the Chastek-paralysis factor. Nor will I engage upon the theme, however attractive, of the phenomenon of adaptation by micro-organisms, the developments of new metabolic pathways in response to the presence of a nutrient, previously unfamiliar to that organism. Cystinuria I begin with cystinuria. In this familial disease, which is possibly inherited as a dominant character, the amino-acid, cystine, is present in quantities much greater than normal in the urine, from which it may be crystallized by appropriate treatment. https://www.cambridge.org/core/terms Garrod (1923) clearly regarded it as an example of arrested metabolism, the subject being supposedly unable to oxidize cystine in the normal way. Even at that time it was known that the urine frequently contained other amino-acids and also the diamine bases, cadaverin and putrescin, in addition to cystine and no explanation could be offered of this fact. Later it was found by Brand, Cahill & Harris (1935) that the giving of cystine to a cystinuric did not raise the output of cystine in the urine, although such a rise did occur after the administration of either cysteine or the other sulphur-containing amino-acid, methionine. Again, it had been observed by Abderhalden (1903) that the . https://doi.org/10.1079/BJN19500040 post-mortem examination of an infant that died at the age of 21 months with symptoms of inanition, revealed the presence of innumerable white specks, shown to be deposits of crystalline cystine, on the surface of the internal organs. The child belonged to Downloaded from 244 CONFERENCEPROCEEDINGS I950 a family which included several cystinurics and, although the presence of cystine in the https://www.cambridge.org/core urine was never demonstrated, this was assumed, also, to be a case of cystinuria. Garrod (1923) comments that in the few other available records of post-mortem examination of cystinurics, no mention is made of such deposits of cystine in the tissues. The whole subject presented a picture of confusion which only began to be dispelled when the technique of partition chromatography became available for the study of pathological urines. Using this powerful tool, Dent (1949) showed that there is a normal . IP address: pattern of amino-acids present in urine (see Fig. I) but that in certain conditions the 170.106.40.139 Normal urine Case A.L. Case S.L. 1 I , on 1s b51 I 0 02 Oct 2021 at 19:20:22 Alanine 0 0 Glutamic acid Glycine 0 , subject to the Cambridge Core terms of use, available at Fig. I Fig. I. Partition chromatogram of amino-acids in normal urine. Fig. 2. Partition chromatogramsof amino-acids in four cystinuric urines. From Dent (1949). I, glutamic acid; 3, glycine; 5, alanine; 12, arginine; 13, lysine; 15, cystine; 17, taurine; 24, unknown, possibly cadaverine or putrescine; 25, unknown; 26, omithine. renal threshold appears to be lowered with a consequent amino-aciduria. Examples of such are the Fanconi syndrome and hepatolenticular degeneration. In the Fanconi https://www.cambridge.org/core/terms syndrome the blood amino-acid nitrogen is within normal limits and the excretion of amino-acids in the urine, including cystine, seems definitely to be due to defective tubular reabsorption.