Identification of 5-hydroxyhexanoic acid in the urine of twin siblings with a syndrome having close similarities to Jamaican vomiting sickness [proceedings].

Jamaican vomiting sickness is characterized by sudden-onset acute vomiting and diarrhoea with profound hypoglycaemia, leading t o coma and death. Pathological changes observed include fatty infiltration of the viscera, and similarities with Reye’s syndrome (encephalopathy and fatty degeneration of the viscera) have been noted (Lowry, 1975). Recently, twin siblings presented in Harrow with a n unusual Reye’s-like syndrome (Whitelaw et al., 1977) associated with an abnormal organic aciduria that had similarities to that observed in patients with Jamaican vomiting sickness (Chalmers et al., 1977), particularly in the nature of the dicarboxylic acids excreted (Chalmers & Lawson, 1977). Jamaican vomiting sickness is caused by the ingestion by infants of unripe ackee fruit, which contains the toxin hypoglycin (L-a-aminomethylenecyclopropylpropionic acid). The association of hypoglycin and Jamaican vomiting sickness has been proved by the occurrence in the urine of two patients with the disease of the glycine conjugate of the active metabolite of hypoglycin, methylenecyclopropylacetic acid (Tanaka et al., 1976). The present paper reports the identification of 5-hydroxyhexanoic acid, a previously unreported urinary organic acid, in the urine of both Harrow patients, which may indicate the underlying aetiology of these cases and the close associations with Jamaican vomiting sickness. Urine was obtained from both siblings on the day of admission to hospital (one urine post mortem) and examined for organic acids by quantitative extraction techniques and g.1.c. and mass spectrometry of the trimethylsilyl derivatives of the extracted acids. Among the most prominent acids observed was one eluted at a retention time relative to n-tetracosane internal standard of 0.39, in the region of organic acids such as the 2,3-dihydroxybutanoic acids (Lawson et al., 1976). Initial low-resolution mass spectrometry showed the acid to be unrecorded in the available library files of spectra and excluded glutaric acid relative retention time 0.42) and ethylmalonic acid (relative retention time0.37), which occur in the urine of patients with Jamaican vomiting sickness (Tanaka et al., 1976). The molecular ion of the trimethylsilyl derivative was a t m/e 276, and this was shown by high-resolution mass spectrometry to have the empirical formula Ci2HZ803Si2 and hence be a monohydroxymonocarboxylic acid. Other prominent ions