A biochemical study of Huntington's chorea.

It is now generally accepted that Huntington's chorea is inherited through a single dominant autosomal gene but apart from this little is known of the aetiology. Earlier investigators had implicated endocrine factors (Mulon and Porak, 1912; Bize, 1934) but without very convincing evidence. With the advent ofnew drugs that had profound effects on the nervous system the idea of a neuronal basis for Huntington's chorea received a fresh impetus but a recent review showed little general agreement (Walter-Buel, 1956). More recently other workers have suggested that the condition could be regarded as a distorted form of psychomotility (Kempinsky, Boniface, Morgan, and Busch, 1960). A recent review of the pathology, after showing that typical changes in the basal ganglia together with non-specific cortical changes are constant features of the condition, ends by suggesting an enzyme deficiency as the responsible factor (McCaughey, 1961). The recent spectacular advances in biochemical genetics had previously led others to speculate on a possible enzymatic aetiology (e.g., Penrose, 1958) but as yet there has been no convincing proof. There are relatively few biochemical studies of Huntington's chorea reported in the literature and in most cases they deal with very small numbers (Falstein and Stone, 1940; Nielsen and Butt, 1955; Forrest, 1957; Chhuttani, Chopra, and Singh, 1959; Oliphant, Evans, and Forrest, 1960; Barbeau, Murphy, and Sourkes, 1961; Williams, Maury, and Kibler, 1961; Perry, 1961). None of these studies has produced any consistently positive findings. Recently there has been a recrudescence of interest in magnesium metabolism and it occurred to one of us (F.E.K.) that it would be worthwhile investigating this in Huntington's chorea, mainly because choreoathetosis and other types of involuntary movements, as well as a variety of abnormal mental states, have been described in patients suffering from disordered magnesium metabolism (British Medical Journal, 1960; Maclntyre, 1960; Lancet, 1960; Hanna, 1961; Wallach, Cahill, Rogan, and Jones, 1962) and on a possible analogy with manganese, which is known to damage the basal ganglia (Cotzias, 1958) but has been shown to be normal in Huntington's chorea (Perry, 1961). MATERIAL AND METHOD