Nephropathic cystinosis is an autosomal recessive lysosomal disease in which 
cystine cannot exit the lysosome to complete its degradation in the cytoplasm, 
thus accumulating in tissues. Some patients develop a distal myopathy involving 
mainly hand muscles. Myopathology descriptions from only 5 patients are 
available in the literature. We present a comprehensive clinical, pathological 
and genetic description of 3 patients from 2 families with nephropathic 
cystinosis. Intrafamiliar variability was detected in one family in which one 
sibling developed a severe distal myopathy while the other sibling did not show 
any signs of skeletal muscle involvement. One of the patients was on treatment 
with Cysteamine for over 12 years but still developed the usual complications of 
nephropathic cystinosis in his twenties. Novel pathological findings consisting 
in sarcoplasmic deposits reactive for slow myosin were identified. Three 
previously known and one novel mutation are reported. Nephropathic cystinosis 
should be included in the differential diagnosis of distal myopathies in those 
with early renal failure. Novel clinical and pathological features are reported 
here contributing to the characterization of the muscle involvement in 
nephropathic cystinosis.