PHENYLPYRUVIC OLIGOPHRENIA

Abstract

PHENYLPYRUVIC OLIGOPHRENIA is an inherited disease characterized by mental deficiency and urinary excretion of phenylpyruvic acid. Patients with this disorder are unable to carry out a particular enzymatic step in the metabolism of phenylalanine; this reaction is the conversion of phenylalanine to tyrosine:[see equation in source pdf]. These individuals therefore appear to be human mutants, analogous to mutants such as those which have been induced in Neurospora crassa and Escherichia coli. However, in contrast to the enzymatic defect in certain mutant microorganisms, which is often recognizable in terms of a specific nutritional requirement, the metabolic block in phenylpyruvic oligophrenia is associated with a relatively complex picture. Phenyipyruvic oligophrenia is a recessive trait; it has been estimated that the gene is carried by approximately 0.5 to 1% of the population. Although most patients with this disease exhibit markedly reduced mental capacity, a few show only moderate retardation. A high percentage of patients with phenylketonuria have fair skin, blue eyes and blond hair. About 25% of patients with phenylpyruvic oligophrenia have experienced seizures, and many of these patients have been reported to show abnormal electroencephalograms. Several necropsies have revealed evidence of abnormal myelination; on the other hand, other postmortem studies have been described as essentially negative. Patients with phenylpyruvic oligophrenia may excrete as much as 1 to 2 gm each of phenylpyruvic acid and phenyllactic acid per day; these compounds are not usually detectable in normal urine (Fig. 1). Urinary excretion of phenylalanine, normally no more than about 30 mg/day, may be as high as 1 gm/day in phenylpyruvic oligophrenia.