Phenylalanine to Tyrosine Ratio Calculator
Phenylalanine to Tyrosine Ratio Calculator
Calculate the phenylalanine to tyrosine ratio used to confirm phenylketonuria on newborn screening, and see when a raised phenylalanine is something else entirely.
Phenylalanine to Tyrosine Ratio
Phe ÷ TyrPhenylalanine 620 µmol/L, tyrosine 48 µmol/L
Formula
- PAH
- phenylalanine hydroxylase — the liver enzyme that converts phenylalanine to tyrosine; deficient in classical PKU
- BH4
- tetrahydrobiopterin, the cofactor PAH requires — its deficiency produces the same biochemical pattern but needs different treatment
- ratio vs phenylalanine alone
- tyrosine falls as phenylalanine rises in true PAH deficiency, so the ratio amplifies both changes and is more specific than phenylalanine alone
Worked example
Phenylalanine 620 µmol/L, tyrosine 48 µmol/L
620 ÷ 48 = 12.92
Above 3 → raised, consistent with PKU
Reading the ratio
| Ratio | Pattern | Consider |
|---|---|---|
| < 2 | Normal | Prematurity, parenteral nutrition, liver disease, early sample |
| 2 – 3 | Borderline | Repeat sample; consider timing and feeding status |
| > 3 | Raised | Classical PKU — urgent confirmatory testing; also consider a BH4 disorder |
Why the ratio, and not phenylalanine alone
Phenylalanine hydroxylase converts phenylalanine to tyrosine in the liver, using tetrahydrobiopterin as a cofactor. When the enzyme is deficient, phenylalanine accumulates while tyrosine — no longer being produced from it — falls or stays low-normal. The ratio of the two amplifies both changes at once and is therefore more specific for the defect than phenylalanine alone.
This distinction matters most in newborn screening, where a raised phenylalanine has several possible explanations besides PKU: prematurity, parenteral nutrition, liver disease, or simply a sample taken before feeding is established all raise it. In those situations tyrosine is normal or even high, so the ratio stays below 2 and does not suggest PAH deficiency.
A raised ratio should prompt urgent confirmatory testing. Untreated classical PKU causes irreversible intellectual disability through the neurotoxic effect of sustained high phenylalanine on the developing brain, and treatment — a phenylalanine-restricted diet — started within the first weeks of life prevents this almost entirely. The screening window is narrow and the consequence of missing it is severe and permanent.
A raised ratio can also indicate a defect of tetrahydrobiopterin synthesis or recycling rather than PAH itself. These BH4 disorders produce the same phenylalanine and tyrosine pattern but need different treatment, since dietary restriction alone does not address the neurotransmitter synthesis defect that accompanies them. Pterin studies and dihydropteridine reductase activity are therefore a routine part of the confirmatory work-up alongside the ratio.
Frequently asked questions
How is the phenylalanine to tyrosine ratio calculated?
Divide the phenylalanine concentration by the tyrosine concentration, both measured in µmol/L on the same sample. A ratio above 3 is considered raised.
Why use a ratio instead of phenylalanine alone?
Because PAH deficiency both raises phenylalanine and lowers tyrosine, the ratio moves further from normal than either value alone, and stays low when a raised phenylalanine has a non-PKU cause.
What causes a raised phenylalanine with a normal ratio?
Prematurity, parenteral nutrition, liver disease, and a sample taken too early after birth all raise phenylalanine without lowering tyrosine, keeping the ratio below 2.
What if the ratio is raised but PAH activity is normal?
Consider a defect of tetrahydrobiopterin synthesis or recycling. These disorders produce the same amino acid pattern but require different treatment, which is why pterin studies and DHPR activity are checked alongside the ratio.
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References
- Vockley J et al. Phenylalanine hydroxylase deficiency: diagnosis and management guideline. Genet Med. 2014;16(2):188–200.
- van Spronsen FJ et al. Phenylketonuria. Nat Rev Dis Primers. 2021;7:36.
Medical Disclaimer: The tools and content provided here are for educational and reference purposes only. They are not intended to substitute for professional medical advice, diagnosis, or treatment. Clinical decisions should always be based on the comprehensive assessment of a qualified healthcare professional.