Phenylketonuria with Normal Intelligence and Gowers' Muscular Dystrophy

Mutations in the phenylalanine hydroxylase gene: genetic determinants for the phenotypic variability of hyperphenylalaninemia

“…Although the mean serum phenylalanine level was identical in patients carrying mutations causing classical PKU compared with patients carrying mutations causing mild PKU, mean IQ was significantly higher in patients with a genotype associated with mild PKU. A significant correlation was found between genotype (classical 10 15 20 25 30…”

“…It is noteworthy that some of these individuals had phenylalanine levels of 400-900 pM (8)(9)(10) Based on determinations of phenylalanine hydroxylase activities in liver needle biopsy specimens, Justice et al (14) demonstrated that two patients with "classic" PKU showed no enzyme activity in the presence of BH4 whereas two clinical variant forms of PKU had 12-50% residual enzyme activity. In an extended study of 43 hyperphenylalaninemic individuals, Bartholome et al (15) showed that patients with classic PKU had no phenylalanine hydroxylase activity in liver needle biopsies, patients with milder forms of PKU showed 6% residual activity and patients with mild hyperphenylalaninemia had 8-35% of normal values.…”

Results of Treatment in Phenylketonuria

“…These are listed in Table I. Case 34 has already been the subject of a paper (Coates, Norman, and Woolf, 1957), and Case 35 is mentioned by Moncrieff and Wilkinson (1961). These are not discussed here.…”

Article Commentary: The contributions of Louis I Woolf to the treatment, early diagnosis and understanding of phenylketonuria

“…In 1957 he suggested this in relation to a six-year-old boy with high serum phenylalanine, low phenylpyruvic acid concentration in urine, and normal intelligence. 49 A year later, in discussing Penrose's calculation that only about 0.1% of phenylketonurics could be in the normal IQ range (an estimate based on the distribution of IQ among institutionalized phenylketonurics), 39 he probably had a semifunctional enzyme in mind when he pointed out that this estimate would not be valid if the distribution of IQ among all individuals excreting phenylpyruvic acid were bimodal. However, it was not until 1966 that he was able to obtain good evidence of the existence of such an enzyme by characterizing the kinetics of phenylalanine metabolism following intravenous phenylalanine injections (a procedure initially developed as a more discriminating test of heterozygosity than the use of oral phenylalanine loading), which with some subjects suggested the presence of a phenylalanine hydroxylase that was abnormally susceptible to inhibition by phenylalanine.…”