Investigations
1st investigations to order
newborn screening for metabolic disorders
Test
Performed on blood spotted onto filter paper (heel-prick test). This should be obtained for all newborn infants at 24 hours of age. An additional test should be obtained no later than 7 days of age if the newborn screen was performed before 24 hours of age, if the newborn is markedly premature, or if the infant is sick and in the intensive care unit.
Result
elevated blood phenylalanine
Investigations to consider
quantitative plasma amino acid analysis
Test
Performed on a plasma or serum sample from whole blood obtained by venipuncture. It will also identify infants with a false-positive newborn screening test who have a normal blood phe on follow-up testing.
Result
distinguishes elevated blood phenylalanine (phe) associated with inherited metabolic disorders from the generalised amino acid elevations observed in association with hepatic dysfunction or marked prematurity
blood dihydropteridine reductase (DHPR) assay
Test
Can be performed on plasma or on blood on filter paper. Inborn errors of tetrahydrobiopterin (BH4) synthesis can also cause hyper-phenylalaninaemia. It is essential to exclude at this stage because treatment for defects in BH4 synthesis is different from treatment for PKU.
Result
excludes DHPR deficiency
urine neopterin to biopterin ratio
Test
Can be performed using a random urine specimen. Inborn errors of BH4 synthesis can also cause hyper-phenylalaninaemia. It is essential to exclude at this stage because treatment for defects in BH4 synthesis is different from treatment for PKU.
Result
identifies defects in BH4 synthesis
mutation analysis of phenylalanine hydroxylase gene
Test
Performed on whole blood sample. May inform about severity and BH4 responsiveness.
Result
identifies specific mutations responsible for the disorder; confirms diagnosis
tetrahydrobiopterin (BH4)-responsiveness test
Test
Plasma or filter paper blood samples for phenylalanine levels are obtained before and at various intervals after giving oral BH4. This test is performed for treatment purposes to find the sub-group of patients with phenylalanine hydroxylase deficiency who are BH4 responsive.[6][7][8]
Result
identifies BH4-responsive patients
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