MALIGNANT HYPERPHENYLALANINEMIA - CLINICAL-FEATURES, BIOCHEMICAL FINDINGS, AND EXPERIENCE WITH ADMINISTRATION OF BIOPTERINS

Four cases of malignant hyperphenylalaninemia (MHPA) are described. Pretreatment serum phenylalanine levels were 1.5, 3.0, 2.4, and 0.9 mmol/l. Dihydropteridine reductase (DHPR) deficiency was proven in 1 patient by assays on cultured fibroblastic cells and was presumed in this patient''s sibling and in another deceased patient, whose parents'' fibroblastic cells show .apprx. 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 tetrahydrobiopterin (BH4) corrected the hyperphenylalaninemia and increased the levels of catecholamines and 5-hydroxy-indoles in the 1 patient studied in life, but BH4 did not reach the CSF. 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 phenylalamine level. The frequency of MHPA in Australia was estimated as 7 in 258 patients with phenylketonuria.