Summary
Huntington disease (HD) is a neurodegenerative disorder of the central nervous system, mainly affecting the basal ganglia (caudate nuclei and putamen). The average prevalence in the general population is 1/16 000. The disease affects females and males indifferently and usually occurs in adults, although at variable ages. Fewer than 10% of cases have juvenile HD, with onset before the age of 20. Onset is often insidious, either with motor abnormalities (choreic syndrome), or with personality or behavioural changes, and even psychiatric disturbances (depression). Alongside the progression of motor disorders leading to falls, dysarthria and difficulties to swallow, dementia sets in. HD is transmitted as an autosomal dominant trait, with penetrance increasing with age. Neomutations can occur, although rarely. The mutation consists in an expansion of a repeated trinucleotide in the IT15 (4p16.3) gene. In very rare cases, mutations in HDL-2 (Huntington disease like 2), SCA17 (spinocereballar ataxia 17) or DRPLA (dentato-rubro-pallido-luysian atrophy) may result in a clinical picture evocative of Huntington disease. Patients with early-stage Huntington disease have recently been shown to have reduced levels of branched chain amino acids (BCAA). Low levels of BCAA indicate energy deficiency, with consequences reaching beyond the central nervous system. The diagnosis is based on cerebral imaging - often showing atrophy of the head of caudate nuclei - and on the genetic analysis. Presymptomatic diagnosis should only be performed in the setting of multidisciplinary team management in healthy at-risk adult individuals who want to know whether they carry the mutation. Prenatal diagnosis can be performed in order to prevent the birth of an affected child. Treatment is symptomatic only (neuroleptics for abnormal movements, psychotropic drugs if needed, physiotherapy). The association of motor and intellectual disorders in patients who are often young adults makes the disease very difficult to manage at home or in institutions. HD progresses slowly and leads to loss of autonomy. Treatments with implants of genetically modified or embryonic cells are currently being assessed. Branched chain amino acid (BCAA) levels may constitute a biomarker of the disease, which could be useful in clinical trials. In addition, correcting the energy deficit could represent a new therapeutic avenue. * Author: Prof. A. Brice (October 2007) *.
