An Inborn Error of Fructose Metabolism

Although essential fructosuria has been known for 70 years and has been recognized as an inborn error of metabolism for more than 20 years (Lasker, 1941), it is only recently that a second metabolic anomaly involving fructose has been described by Froesch, Prader, Labhart, Stuber and Wolf (1957). These authors recorded four affected (two children and two adults) and three probably affected members of a large family in which intermarriage had been frequent. This condition of fructose intolerance, although similar in some respects to essential fructosuria, differed in that ingestion of fructose or fructose-containing foods caused a sharp and prolonged fall in the blood glucose level accompanied by the clinical symptoms of severe hypoglycaemia. The continued ingestion of fructose in infancy could result in retarded growth and mental development. Subsequently, Froesch, Prader, Wolf and Labhart (1959) suggested that, in essential fructosuria, the metabolic anomaly lay in a deficiency of the hepatic fructokinase (Fig. 1) which converts the fructose to fructose-l -phosphate, whereas in fructose intolerance there was an absence or deficiency of fructose-lphosphate aldolase, cleaving fructose-l-phosphate to glyceraldehyde and dihydroxyacetone phosphate (Fig. 1). This hypothesis was based mainly on the prolonged fall in serum phosphate which occurred on fructose administration, indicating that the conversion of fructose to fructose-1-phosphate by the specific fructokinase had proceeded normally, with accumulation of the phosphate in the cell. The clear recognition of this syndrome has been rapidly followed by several further reports of cases (Wolf, Zschocke, Wedemeyer and Hubner, 1959; Dormandy and Porter, 1961; Dubois, Loeb, Ooms, Gillet, Bartman and Champenois, 1961; Jeune, Planson, Cotte, Bonnefoy, Nivelon and Skosowsky, 1961; Nikkilii, Somersalo, Pitkanen and Perheentupa, 1962). In four instances, one other member of the family was affected by the same metabolic abnormality but less severely. We now record three further examples of this condition, two sibs of one family and the third in an unrelated family. The younger of the two sibs was admitted to hospital at 7 weeks of age because of reluctance to take feeds, lethargy and severe weight loss. The presence of fructose in the urine on many occasions, so long as the patient was on feeds containing sucrose, led to the diagnosis. Examination of the rest of the family revealed another affected child, normal in intelligence and growth. The investigations described in this article afford further evidence for the suggested underlying metabolic anomaly in this condition and also show the clinical and biochemical similarity between it and galactosaemia, for which reason we prefer to call it fructosaemia, rather than fructose intolerance. As these cases were discovered within a period of a few months of each other, it is likely that the condition is more common than was at first thought and because it may lead to mental and physical retardation and underdevelopment, it is important that it should be recognized as early as possible, since it is easily treated.