BIOCHEMICAL CONTROL, GENETIC-ANALYSIS AND MAGNETIC-RESONANCE-IMAGING IN PATIENTS WITH PHENYLKETONURIA

Thirteen patients with phenylketonuria, detected by neonatal screening and started on diet within 16 days of age, were investigated between 10 and 18 years of age by magnetic resonance imaging (MRI) of the brai n. Biochemical control was assessed from: (1) the life time blood phen ylalanine (Phe) control (as determined from (a) the mean yearly exposu re to Phe; (b) the accumulated time for each patient that Phe was < 12 0 mumol/l; (c) > 400 mumol/l; (d) > 800 mumol/l; and (e) > 1200 mumol/ l); and (2) the blood Phe control over the 5 years prior to imaging (a ssessed for each patient by the mean yearly Phe exposure over that per iod). In all patients the phenylalanine hydroxylase gene locus was stu died using restriction fragment length polymorphism haplotypes and mut ant genes were screened for a variety of specific mutations which have been reported in other European populations or in populations of nort h European descent. Two patients had significant abnormalities of cere bral white matter. Although both showed poor biochemical control this did not reach statistical significance when compared to those with nor mal imaging. DNA haplotype patterns could be assigned to 11 patients a nd mutant genes were identified in 12. One patient with abnormal imagi ng and 4 patients without abnormalities had mutations on both chromoso mes identified. In these 5 patients there was significant correlation between their genotype and biochemical control. Mutations resulting in residual in vitro enzyme activity were associated with normal imaging .