Comparative diagnostic value of phenyla‐lanine challenge and phenylalanine hydroxylase activity in phenylketonuria

Abstract

Serum phenylalanine (phe) concentrations during and following phe challenges and liver phenylalanine hydroxylase (PH) activity were compared in 13 phenylketonuric (PKU) patients. These patients were separated into two groups: eight patients with no detectable PH activity (PH°) and five patients with residual PH activity (PH‐) ranging from 9 to 24% of the activity obtained in 10 non‐PKU subjects. The rise in serum phe concentration during 3 days of oral loading did not differentiate the two groups. However, the difference in serum phe concentration of the PH° and PH‐ groups reached statistical significance at 24 h postloading (p<0.01). We concluded that combined results from multiple measurements during the oral challenge, namely serum phe concentration after termination of loading, serum phe clearance rate, post‐loading phe tolerance index and urinary metabolite excretion, make a better indicator for predicting residual PH activity for the majority of PKU subjects than peak phe concentrations during phe challenge.

Diagnosis, classification, and genetics of phenylketonuria and tetrahydrobiopterin (BH4) deficiencies

“…Because these variants were initially thought not to require dietary treatment, a reliable discrimination of these phenotypes was needed. For practical and ethical reasons, in vivo 3 H or 14 C isotope studies [30] or invasive testing such as enzyme assays from liver biopsies [31] were not appropriate. Therefore, Blaskovics [32] developed in the mid-1960s the standardized three day natural protein loading test with evaporated milk that was applied at 6 months of age in the U.S. [33] and German [34] PKU Collaborative Studies for classification of PKU and for genotype-phenotype analysis.…”

Beneficial Effects of Slow-Release Large Neutral Amino Acids after a Phenylalanine Oral Load in Patients with Phenylketonuria

“…Indeed, 86% of the patients had severe PAH mutations with null or very low predicted enzyme activity and poor capability of Phe clearance. During the late 1970s and 1980s, Phe-loading tests with high Phe oral doses were conducted in infant dietary treated PKU patients to discriminate between classic or variant PKU, inducing picks up to 2000 µmol/L of plasma Phe followed by slow plasma Phe clearance after 48-72 h [41][42][43]. Assuming that the more physiological absorption of srLNAAs could minimize the increase in plasma Phe, particularly in the morning, we considered it safer to perform dietary Phe increases only in combination with srLNAAs.…”