Homocarnosinosis

Homocarnosinosis is an extremely rare inborn error of metabolism characterized by elevated levels of homocarnosine (gamma-aminobutyryl-histidine) in the cerebrospinal fluid (CSF) and, in some cases, in the urine. Homocarnosine is a dipeptide found predominantly in the brain, and its accumulation is thought to reflect a deficiency in homocarnosinase activity, the enzyme responsible for its degradation. The condition primarily affects the central nervous system. The disorder was first described in a Norwegian family and has been associated with progressive spastic paraplegia, intellectual disability, and retinal pigmentation. Additional neurological features may include seizures and variable degrees of cognitive impairment. However, the clinical significance of elevated homocarnosine levels remains debated, as some individuals with biochemical findings have been reported without overt neurological symptoms, raising questions about whether homocarnosinosis is truly pathogenic or a benign biochemical variant. There is no specific treatment for homocarnosinosis. Management is supportive and symptomatic, focusing on neurological manifestations such as spasticity and seizures. Physical therapy and rehabilitation may be beneficial for individuals with motor impairment. Genetic counseling is recommended for affected families. Due to the extreme rarity of this condition, knowledge about its natural history and long-term prognosis remains very limited.

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