Four-hydroxyphenylpyruvic acid oxidase deficiency with normal fumarylacetoacetase: a new variant form of hereditary hypertyrosinemia

Abstract

Enzymatic studies on the liver of an infant are described-a case of hypertyrosinemia without hepatic dysfunction. His parents were siblings and the mother had hypertyrosinemia. Excessive amounts of 4-hydroxyphenylpyruvic acid (pHPP), 4-hydroxyphenylacetic acid (pHPL), and 4-hydroxyphenylacetic acid (pHPA) were found to be excreted in the patient's urine as well as in the urine of the mother and the inhibitor of porphobilinogen synthetase was not found. Soluble tyrosine aminotransferase (s-TAT), separated from that of the mitochondrial form (m-TAT) by DE 52 column chromatography, was normal in the patient's liver, both quantitatively and qualitatively. The activities of fumarylacetoacetase in the patient's liver and in the peripheral leucocytes from the parents were normal. The activity of pHPP oxidase in the patient's liver was approximately 5% of the control and the enzyme had a high Km value for pHPP (controls: 0.06 +/- 0.01 mM, patient: 0.23 +/- 0.03 mM). From these results, the patient was thought to be different from previously described types of tyrosinemia and perhaps representative of a new variant form. This is the first report concerning 4-hydroxyphenylpyruvic acid oxidase deficiency alone. Mild metal retardation and mild hypertyrosinemia may be offered as typical clinical features of the disease.