Rationale for the German recommendations for phenylalanine level control in phenylketonuria 1997

Treatment of hyperphenylalaninaemias due to phenylalanine hydroxylase defic iency with a low phenylalanine (Phe) diet is highly successful in preventin g neurological impairment and mental retardation. There is consensus that, for an optimal outcome, treatment should start as early as possible, and th at strict blood Phe level control is of primary importance during the first years of life, but for adolescent and adult patients international treatme nt recommendations show a great variability. A working party of the German Working Group for Metabolic Diseases has evaluated research results on IQ d ata, speech development, behavioural problems, educational progress, neurop sychological results, electroencephalography, magnetic resonance imaging, a nd clinical neurology. Based on the actual knowledge, recommendations were formulated with regard to indication of treatment, differential diagnosis, and Phe level control during different age periods. The development of the early-and-strictly-treated patient in middle and late adulthood still remai ns to be investigated. Therefore, the recommendations should be regarded as provisional and subject to future research, Efficient treatment of phenylk etonuria has to go beyond recommendations for blood Phe level control and m ust include adequate dietary training, medical as well as psychological cou nselling of the patient and his family, and a protocol for monitoring outco me. Conclusions Early-and-strictly-treated patients with phenylketonuria show a n almost normal development. During the first 10 years treatment should aim at blood Phenylalanine levels between 40 and 240 mu mol/L. After the age o f 10, blood phenylalanine level control can be gradually relaxed. For reaso ns of possible unknown late sequelae, all patients should be followed up li fe-long.