PROBLEMS OF A MUSCLE DISEASE 



creatinine formation represents a type of endogenous metabolism dis- 

 tinct from the exof^enous metabolism of food protein (5) is no longer 

 tenable, as a result of the studies performed by Bloch and Schoen- 

 heimer with the aid of isotopic nitrogen (14). The constant daily 

 excretion of creatinine, in contrast to the highly inconstant excretion 

 of other nitrogenous constituents of the urine, however, indicates that 

 the formation of creatinine is an orderly and well-regulated process, 

 the biological significance of which is not entirely apparent. That it 

 arises directly from creatine is abundantly clear. Moreover, there is 

 recent evidence to indicate that it arises in the process of dcphosphoryl- 

 ation of creatine phosphate, and that its formation is intimately con- 

 nected with the phenomenon of muscular activity (2,13). 



The marked decrease in the output of creatinine observed con- 

 sistently in patients with progressive muscular dystrophy has been 

 attributed to a reduction in the total mass and cfTiciency of the mus- 

 cular system in this disease. In the normal subject there is a rather 

 remarkable relationship between the level of urinary creatinine and 

 the total mass of the musculature. By taking the muscle mass of the 

 normal subject as 43% of the body weight, a fairly quantitative idea 

 of the mass of functioning muscle in patients with progressive muscular 

 dystrophy can be obtained from a consideration of the value of the 

 urinary creatinine. This value has been found to vary from 35 to 

 40% in cases of incipient progressive muscular dystrophy to values as 

 low as 17% in patients in whom the disease was advanced. In our 

 laboratory, a marked correlation has been observed consistently be- 

 tween the muscle mass calculated as per cent of body weight and the 

 degree of physical performance of patients with dystrophy, in so far 

 as such performance could be appraised in a quantitative fashion. 

 Calculation of the muscle mass on the basis of creatinine excretion 

 appears to yield important information regarding the extent to which 

 the muscular system is involved in patients with this disease. More- 

 over, by performing this type of calculation at frequent intervals on a 

 given subject with progressive muscular dystrophy, a fairly quantita- 

 tive appraisal of the clinical condition of the patient and the rate of 

 progression of the disease at various intervals can be ascertained. 



Following the elucidation of the role of methionine in the syn- 

 thesis of creatine and creatinine by Bloch and Schoenheimer (1) and 

 du Vigneaud (19), speculation arose in the laboratory over the possi- 



421 



