Lychees causing seasonal encephalopathy

Since 1995, there have been annual outbreaks in Muzzafurpur, India, of an acute, often fatal encephalopathy affecting mainly rural children from poor socio-economic backgrounds. Seizures often commenced early morning in previously well children. Postulated causes included viral encephalitis and heat-stroke. However, initial investigations suggested hypoglycaemia was common. Muzzafurpur is a lychee-growing area and previous reports from Vietnam described an association between lychees and acute encephalitis. This hypothesis was explored in a collaborative case–control study conducted by the Indian and US Centres for Disease Control of 390 children <15 years hospitalised with acute encephalopathy, of whom 122 (31%) died. On admission, more than half the patients (171; 52%) had glucose concentrations ≤2.78 mmol/L (≤50 mg/ dL). When 104 cases were compared with 104 age-matched hospital controls, lychee consumption was strongly associated with illness (matched odds ratio 9.6; 95% CI 3.6–24). Children who had no evening meal were significantly more likely to be affected. Tests for infectious agents and pesticides were negative. Toxic metabolites (hypoglycin A and MCPG) are present in high concentrations in unripe lychees, and are known to affect β-oxidation of fatty acids and gluconeogenesis. These toxins were detected in urine specimens from 66% of cases – but no controls. Apart from hypoglycaemia, 90% of cases had abnormal plasma acylcarnitine profiles, consistent with severely disrupted fatty acid metabolism. Preventative measures, advising parents to limit children’s lychee consumption and to ensure an evening meal, have greatly reduced emergency department presentations and death.