Sjaastad et al. (1976) found levels of homocarnosine, a brain-specific dipeptide of gamma-aminobutyric acid (GABA) and histidine, elevated to about 20 times normal in 2 brothers and a sister. All 3 had progressive spastic paraplegia, mental retardation and ... Sjaastad et al. (1976) found levels of homocarnosine, a brain-specific dipeptide of gamma-aminobutyric acid (GABA) and histidine, elevated to about 20 times normal in 2 brothers and a sister. All 3 had progressive spastic paraplegia, mental retardation and retinal pigmentation. The mother was clinically normal but had elevated CSF homocarnosine in a range even higher than that of the affected children. Carnosine is found mainly but not exclusively in muscle. Other families with spastic paraplegia did not show increased concentrations of CSF homocarnosine (Sjaastad et al., 1977). In the Norwegian family of Sjaastad et al. (1977), Perry et al. (1979) demonstrated deficiency of homocarnosinase in the brain. The neurologic normality of the mother makes the relationship of homocarnosinosis to the disorder in the sibs problematic. Lunde et al. (1982) found hypercarnosinuria in patients with homocarnosinosis. Lenney et al. (1983) concluded that homocarnosinase is not present in normal brain tissue; that serum carnosinase, which hydrolyzes homocarnosine about 5% as rapidly as it splits carnosine, is present in normal CSF but absent from the CSF of a homocarnosinosis patient; and that elevation of CSF homocarnosine in this disorder is attributable to serum carnosinase deficiency. The relationship to carnosinemia (212200) requires elucidation. Lunde et al. (1986) showed that histidine in the CSF, plasma and urine could be reduced by about 90%, CSF homocarnosine reduced by about 70%, and urinary carnosine reduced by lesser amounts when the subjects were maintained on a low-histidine diet. The clinical neurologic symptoms were unaltered, however.