Some Biochemical Effects of Chloral Hydrate in an Infant with a Tyrosinemia-like Syndrome

Extract: An infant with a combination of clinical and biochemical features resembling those found in hereditary tyrosinemia (“inborn hepatorenal dysfunction with tyrosyluria”) but with spontaneous recovery is described briefly. The child also had severe congenital hydrocephalus, and was being given chloral hydrate. She was not treated by restriction of dietary phenylalanine and tyrosine. The abnormal aromatic aciduria was unaltered by ascorbic acid administration. The results of loading tests with phenylalanine, tyrosine, and sodium 4-hydroxyphenylpyruvate are compatible with the existence of a partial block in the oxidation of 4-hydroxyphenylpyruvate to homogentisate which was exacerbated by administering chloral hydrate. Speculation: It is suggested that an abnormality of the patient's 4-hydroxy-phenylpyruvate dioxygenase (EC. 1.13.11.27) system rendered it susceptible to inhibition by chloral hydrate or its metabolites in vivo. Such an abnormality could be due to a genetically determined abnormality of the enzyme protein or exposure to an unidentified infective or toxic agent in utero.