Hereditary fructose intolerance is a recessively-transmitted disorder of metabolism caused by deficiency of
aldolase B in the liver, intestine and kidney, that responds favourably to an exclusion diet. The occurrence of fatal hepatorenal failure in a 16-year-old girl, who had received infusions of
fructose and
sorbitol during
minor surgery, led us to suspect that she had suffered from
hereditary fructose intolerance. Molecular analysis of leucocyte
DNA obtained from her brother who had had a long-standing aversion to fruit and
sugar, showed two previously unknown mutations in the
aldolase B gene. An
initiation codon mutation, M-1T, was inherited from the father, whereas Y203X, inherited from the mother, is a
nonsense mutation that replaces a
tyrosine codon by the ochre termination signal. The only source of genomic
DNA from the index case was a fixed fragment of necrotic liver that had been obtained by needle aspiration postmortem and was embedded in
paraffin wax. Analysis of
aldolase B genes in this sample by procedures based on the polymerase chain reaction (PCR) confirmed the presence of both mutations in the proposita, the diagnosis of
hereditary fructose intolerance, and the cause of death.