Significance of the in vivo deuterated phenylalanine load for long-term phenylalanine tolerance and psycho-intellectual outcome in patients with PKU.

In 20 patients with PAH deficiency, in vivo RA was determined by an intravenous deuterated Phe load. Sixteen patients had RAs of less than 0.4% of normal, 3 a clearly detectable activity between 0.8 and 1.4% of normal. Long-term Phe tolerance as measured by the distribution of plasma Phe levels in categories (0-3.9, 4.0-9.9, 10-15.9 and over 16 mg/dl) was much improved in patients with RAs greater than 0.8%. There was a negative correlation between RA and number of plasma Phe levels greater than 16 mg/dl. Relationship between full scale IQ at the age of 9 years and dietary control showed a positive correlation between IQ and the number of Phe levels between 0-10 mg/dl (k = .50 p less than 0.05). Highest (negative) correlation (k = -0.67 p less than 0.007) was found between full scale IQ and the number of Phe values greater than 16 mg/dl as measured over 9 years. On the one hand detectable RA of PAH reduces the risk of high Phe levels and thus may also reduce the risk of brain damage in untreated or suboptimally treated patients with PAH. On the other hand enzyme measurement of PAH is no predictive parameter for Phe tolerance in an individual patient since RA may be very similar in phenylketonuric/hyperphenylalaninaemic patients. For practical purposes the oral protein loading test at the age of 6 months will give the most reliable results for differential diagnosis of PAH deficiency.