Histidinaemia: a child and his family.

Histidinaemia, an inherited disorder of histidine metabolism, was first described by Ghadimi, Partington, and Hunter in 1961. The principal metabolic pathway for histidine is through urocanic acid and formiminoglutamic acid (FIGLU) to glutamic acid (Fig. 1). Zannoni and La Du (1963) demonstrated that histidase, the enzyme necessary for the conversion of histidine to urocanic acid, was absent from skin homogenates of patients with histidinaemia. The absence of histidase usually leads to the breakdown of histidine by an alternative pathway, to imidazolepyruvic acid, imidazoleacetic acid, and imidazolelactic acid. The imidazolepyruvic acid thus formed is excreted in the urine and gives a positive result with the 'Phenistix'* and ferric chloride tests (Auerbach, DiGeorge, Baldridge, Tourtellotte, and Brigham, 1962; Barger and Stewart, 1926). The majority of cases of histidinaemia have been discovered by this means, and in many this has led to a presumptive diagnosis ofphenylketonuria. Davies and Robinson (1963) described a boy in whom the urinary ferric chloride test only became positive after a histidine load. We report here another patient in whom the ferric chloride test was negative and in whom the excretion of abnormal imidazole compounds was undetectable by chromatographic means, even after