Disorders of Histidine Metabolism
The primary disorders of histidine metabolism are histidinemia and urocanase deficiency (urocanic aciduria).
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Disorders of Histidine Metabolism YASUHIRO KURODA, MICHINORI ITO
Introduction
The primary disorders of histidine metabolism are histidinemia and urocanase deficiency (urocanic aciduria). Histidinemia is an autosomal recessive disorder that is benign in most affected individuals. The incidence from newborn screening is 1: 10 ODD, making histidinemia one of the most frequent of the inborn errors of metabolism. The enzyme defect is histidase, an enzyme normally expressed only in skin and liver. The block in conversion of histidine to urocanic acid results in an increased concentration of histidine in blood and urine and the abnormal presence of histidine metabolites in urine. There is biochemical heterogeneity in histidinemia, as there is in other inborn errors of metabolism. There are two groups with respect to residual skin histidase activity. One group, the larger, is characterized by the lower residual enzyme activity and the other group by the higher activity. Lower fasting blood histidine levels and higher tolerances to dietary histidine correspond to the higher residual histidase activity in the second group. However, there were no differences between the two groups in clinical phenotypes. The diagnosis of histidinemia is based on finding an elevation of histidine in the blood and increased excretion of histidine and imidazolepyruvic acid in the urine. The urinary metabolite, imidazolepyruvic acid, can usually be detected by the ferric chloride test or by dipping the Phenistix reagent strip into the urine. The diagnosis is confirmed by demonstrating the absence or marked reduction of histidase activity in skin or the absence of urocanic acid in skin. Treatment with a histidine-restricted diet normalizes the biochemical phenotype but is not indicated for this probably harmless disorder although the treatment might be considered in any histidinemic infant who also has clinical abnormalities. Urocanase deficiency is a very rare autosomal recessive disorder that may be benign in most affected individuals. The reported cases with the disorder are less than ten. The enzyme defect is urocanase, an enzyme normally expressed in liver. The block in conversion of urocanic acid to imidaN. Blau et al. (eds.), Physician’s Guide to the Laboratory Diagnosis of Metabolic Diseases © Springer-Verlag Berlin Heidelberg 2003
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Disorders of Histidine Metabolism
zolonepropionic acid results in a greatly increased concentration of urocanic acid in urine, while histidine and histidine metabolites are normal or only mildly increased. The diagnosis of urocanase deficiency is based on finding increased excretion of urocanic acid in the urine. A histidine loading test exaggerated the urocanic acid excretion and also lead to the production of imidazolepropionic acid, a byproduct of urocanic acid. Metabolites such as imidazolonepropionic acid and formiminoglutamic acid, which are distal to the metabolic step catalyzed by urocanase, were not present in urine after loading with histidine. The diagnosis of a urocanase deficiency is confi
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