APPENDIX TO URINE 569 



4. INBORN ERRORS OF METABOLISM. 



Under this title A. E. Garrod has grouped together four anomalies in 

 metabolism, namely, albinism, alkaptonuria, cystinuria, pentosuria. These 

 anomalies are of life-long persistence and in most cases are inborn. They 

 may occur as temporary phenomena in disease. 



(1) Albinism. 



The essential phenomenon of albinism is the absence of pigments of the 

 melanin group which play the chief part in the coloration of man and the 

 lower animals. All varieties of melanins are absent in albinos white hair, 

 pink eyes, unpigmented skin. 



The lipochrome pigments which colour fats, serum, etc., yellow are not 

 absent. 



(2) Alkaptonuria. 



This is the best-known example of an inborn error. It is rendered 

 evident by the freshly passed urine of an alkaptonuric beginning to darken 

 on exposure to the air, due to absorption of oxygen. The darkening com- 

 mences at the surface and gradually spreads through the liquid until it 

 assumes a black colour. Alkali greatly hastens the darkening. 



The urine, heated with Fehling's solution, gives a deep brown colour and 

 there is a copious reduction. The colour of the liquid differentiates it from 

 the reduction produced by other substances. Ammoniacal silver nitrate 

 solution is rapidly reduced in the cold. Nylander's reagent is darkened, but 

 there is no reduction to bismuth. A yellow precipitate is formed when such 

 urine is treated with Millon's reagent. The most striking reaction is given 

 with ferric chloride. If the reagent be allowed to fall drop by drop into the 

 urine, a momentary deep blue colour appears ; this can be continued until 

 oxidation is complete. 



The first case of alkaptonuria was described by Marcet in 1823 ; in 1858 

 Bodeker showed that the reducing substance was not glucose. Wolkow and 

 Baumann in 1891 clearly established that the peculiar body in the urine was 

 homogentisic acid (hydroquinone acetic acid, p. 271). 



It is derived from the aromatic compounds tyrosine and phenylalanine 

 in the protein food and probably represents a stage in their catabolism in 

 the body. 



(3) Cystinuria. 



Cases of cystinuria are characterised by the deposits of cystine crystals 

 in the form of hexagonal plates in the urine. The odour of hydrogen 

 sulphide may become apparent when the urine decomposes. 



The first case was that described by Woliaston in 1810, who obtained a 

 cystine calculus from the bladder of a child. The phenomenon is believed 

 to be the most common of the inborn errors, but is difficult of recognition. 



It is also apparently due to incomplete oxidation of protein, especially 

 the cystine unit. Frequently the diamines, putrescine and cadaverine, more 

 rarely leucine and tyrosine, are found with cystine in the urine. 



(4) Pentosuria. 



The first case of the excretion of a pentose in the urine was described by 

 Salkowski and Jastrowitz in 1892. Several cases have since been recorded. 

 Though the urine reduced Fehling's solution, it did not ferment with yeast 

 and was optically inactive. An osazone melting at 159 was isolated; 

 glucosazone melts at 205. The presence of pentose can be confirmed by 

 the phloroglucinol and orcinol tests (see p. 196). 



