Significance of the in vivo deuterated phenylalanine load for long-term phenylalanine tolerance and psychointellectual 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, 3a 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 >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=.50p<0.05). Highest (negative) correlation (k=−0.67p<0.007) was found between full scale IQ and the number of Phe values >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.
Key wordsPKU Phenylalanine hydroxylase Deuterated phenylalanine Psychointellectual outcome
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