Malignant hyperphenylalaninemia—clinical features, biochemical findings, and experience with administration of biopterins

Abstract

Four cases of malignant hyperphenylalaninemia (MHPA) are described. Pretreatment serum phenylalanine levels were 1.5, 3.0, 2.4, and 0.9 mmoles/1. Dihydropteridine reductase (DHPR) deficiency was proven in one patient by assays on cultured fibroblastic cells and was presumed in her sibling and in another deceased patient whose parents’ fibroblastic cells show approximately 50% of normal enzyme activity. DHPR and phenylalanine hydroxylase deficiency were excluded by assays on liver obtained at autopsy in the 4th patient. Parenteral administration of tetrahydrobiopterir. (BH4) corrected the hyperphenylalaninemia and increased the levels of catecholamines and 5-hydroxy-indoles in the one patient studied in life, but BH4 did not reach the cerebrospinal fluid. A 3- wk course of BH4 therapy had no clinical effect. Oral biopterin was absorbed and excreted in the urine, but did not alter the serum phenylalanine level. The frequency of MHPA in Australia was estimated as 7 in 258 patients with phenylketonuria. Speculation: Response of serum phenylalanine to a single injection of BH4 appears to be the most simple method of diagnosis of MHPA, applicable to all newly diagnosed cases of PKU, provided the pharmaceutical industry can be persuaded to make small quantities of this compound available. © 1979 International Pediatric Research Foundation, Inc.