ALKAPTONURIA 503 



The anomaly is chronic and, persists throughout life in those patients 

 who were thoroughly investigated and whose histories are authentic. It 

 seems more common in males than in females. There are those who have 

 reported alkaptonuria of a transitory nature in patients suffering from 

 other diseases. Zimnicki reported a case of intermittent alkaptonuria 

 in a patient who had hypertrophic cirrhosis of the liver; Geyger in a 

 case of diabetes; Slosse in a pyonephritic individual, von Moraczewski(a) 

 in a case of tuberculosis, and C. Hirsch in a girl IT years of age who 

 for three days passed an alkapton urine while suffering from a febrile 

 gastro-enteritis. 



To Boedeker(a) (1859) is due the honor of naming the anomaly here 

 discussed and describing its characteristics. It was Marshall, however, 

 who in 1887, isolated the alkapton substance from the urine and called it 

 glycosuric acid. Previous to Marshall, Ebstein and Mliller in 1875 found 

 in the urine of a child pyrocatechol which they thought was the alkapton 

 substance of Boedeker. A urine containing pyrocatechol will turn dark 

 if exposed to the air, especially if the reaction is alkaline. It will also 

 reduce copper solutions. 



Fleischer and Smith ascribed the alkapton properties of the urine 

 to protocatechinic acid. Before coming to the actual substance found 

 in the urine of alkaptonurics, we wish to dismiss with a few words the 

 question of the presence of uroleucic acid in the urine of alkaptonurics. 

 Kirk (a.) described in 1886 a substance which he isolated from urine of 

 alkaptonuric patients. This substance melted at 133.3 C., whereas 

 homogentisic acid melts at 146-147 C. While the results of Kirk were 

 confirmed by Huppert and by Langstein and Meyer, Garrod and Hurtley, 

 reviewing the entire subject critically, deny the existence of such a sub- 

 stance in the urine. In fact, Kirk expressed the opinion that his so- 

 called "uroleucic" acid was impure homogentisic acid. It is curious to 

 note that Hurtley, in translating Carl ISTeuberg's chapter on the "Rarer 

 Disturbances of Protein Metabolism," makes no mention of the conclu- 

 sion of the absence of such a substance as uroleucic acid, and states: 

 "In addition, a second aromatic dioxy acid found by Kirk is also occa- 

 sionally present." 



It was, however, in 1891 that Wolkow and Baumann isolated homo- 

 gentisic acid from a case of alkaptonuria. This acid crystallizes with 

 1 molecule of water in large, transparent, prismatic crystals, which lose 

 their transparency with the loss of the water of crystallization. They 

 melt at 146.5-147 C. They are soluble in water, alcohol, ether, and 

 nearly insoluble in chloroform and benzene. With Millon's reagent, 

 the acid gives a lemon colored precipitate, reduces Fehling's, is optically 

 inactive and is non-fermentable. With benzoyl chlorid and sodium 

 hydroxid in the presence of ammonia, Orton and Garrod obtained the 

 amid of dibenzoylhomogentistic acid, which melts at 204 C., a reac- 



