Histopathology of the nervous system in carnosinase enzyme deficiency with mental retardation

A few years ago, Perry e t al.’ reported a heretofore unknown metabolic disorder associated with progressive motor dysfunction, mental retardation, deafness, and blindness in two siblings who had appeared normal during the first few months of life. In the course of their physical and mental deterioration, which h a d b e e n initiated by seizures, increased amounts of carnosine were found in the urine and an elevated carnosine concentration in the serum and a deficiency of serum carnosinase activity were demonstrated.2 These higherthan-normal levels of serum carnosine persisted even when the children were on diets free of meat products. Recently, two physically and mentally retarded boys were observed in the follow-up studies of infants born a t the Children’s Hospital (in the Child Development Program) with a disease pattern similar t o that described by Perry e t al. The boys were severely mentally retarded; however, their younger sister appeared normal. In all three siblings carnosinuria, carnosinemia, and serum carnosinase deficiency were demonstrated. Extracts of liver, kidney, and spleen obtained after death of the older boy were examined by electrophoresis. There was only one of the two forms of carnosinase normally present in these tissues. In the sera of the parents carnosinase activity was detectable but a t a lower level than normal. (A detailed account of the methods used for the assay of the enzyme carnosinase will be given elsehere.^) We shall report briefly the clinical history of