Dietary treatment of homocystinuria.

Homocystinuria was described in 1962 by Field, Carson, Cusworth, Dent, and Neil and later in the same year by Gerritsen, Vaughn, and Waisman. A further case was reported by Komrower and Wilson (1963); in this case and the ones described by Field et al., the patients presented a characteristic picture of congenital bilateral dislocation of the eye lens, iridodenesis, genu valgum, pes planum, and kyphoscoliosis. They had fair brittle hair (though some later cases lack this feature (Schimke, McKusick, Huang, and Pollack, 1965), a high malar flush, and showed evidence of poor peripheral blood circulation. Vascular thromboses have been reported by several observers and we have seen three examples of this complication; two children died following operations to relieve intraocular tension and were found, at necropsy, to have a pulmonary embolism. All of the early cases showed mental retardation, but several cases reported by Schimke et al. have normal intelligence. Carson, Cusworth, Dent, Field, Neill, and Westall (1963) studied the first reported case in more detail and carried out biochemical investigations, showing that there was an increased level of methionine and a readily detectable level of homocystine in the blood plasma, and an increased excretion of these sulphur-containing amino acids in the urine. Moreover, the urinary homocystine was isolated in crystalline form and subjected to chemical analysis to confirm its identity. Gerritsen and Waisman (1964) reported on the absence of cystathionine in the brain of their first patient who had died of the disease and this observation was confirmed by Brenton, Cusworth, and Gaull (1965) who examined the brain in a further fatal case. As a result of these observations it was suggested that the clinical picture of the disease arose from a failure to convert methionine to cystine, due to the lack of a specific enzyme. Mudd, Finkelstein, Irreverre, and Laster (1964) demonstrated extremely low activity of cystathionine synthetase in liver tissue obtained