Detection of heterozygous carriers for phenylketonuria by a L-[2H5]phenylalanine stable isotope loading test

Oral loading with 25 mg/kg of pentadeuterated L-phenylalanine has been used for the discrimination between normozygous subjects and carriers for phenylketonuria. The test provides five types of data derived from plasma Phe and Tyr concentrations on which the discrimination can be based: fasting phenylalanine/tyrosine ratios, total Phe levels, total Phe/total Tyr ratios, absolute L-[2H5]phenylalanine plasma levels, and L-[2H5]Phe/L-[2H4]Tyr ratios. Absolute L-[2H4]Tyr and total L-Tyr concentrations provide the poorest discrimination with statistical classification errors around 30%. The corresponding classification error of fasting Phe/fasting Tyr ratios was circa 13%, and both labelled Phe/labelled Tyr and total Phe/total Tyr concentration ratios gave minimal errors below 2%.