|Values are valid only on day of printing.|
Phenylketonuria (PKU) is the most frequent inherited disorder of amino acid metabolism (about 1:10,000-1:15,000) and was the first successfully treated inborn error of metabolism. It is inherited in an autosomal recessive manner and is caused by a defect in the enzyme phenylalanine hydroxylase (PAH), which converts the essential amino acid phenylalanine to tyrosine. Deficiency of PAH results in decreased levels of tyrosine and an accumulation of phenylalanine in blood and tissues. Untreated, PKU leads to severe brain damage with intellectual impairment, behavior abnormalities, seizures, and spasticity. The level of enzyme activity differentiates classic PKU (PAH activity <1%) from other milder forms; however, all are characterized by increased levels of phenylalanine (hyperphenylalanemia). Treatment includes the early introduction of a diet low in phenylalanine.
Tetrahydrobiopterin (BH4) is a cofactor of not only PAH, but also of the tyrosine and tryptophan hydroxylases. Approximately 2% of patients with hyperphenylalanemia have a deficiency of BH4, which causes a secondary deficit of the neurotransmitters dopamine and serotonin. There are 4 autosomal-recessive disorders associated with BH4 deficiency plus hyperphenylalanemia; guanosine triphosphate cyclohydrolase deficiency, 6-pyruvoyl tetrahydropterine synthase deficiency, dihydropteridine reductase deficiency, and pterin-4 alpha carbinolamine dehydratase (PCD) deficiency. This group of disorders, with the exception of PCD, is characterized by progressive dystonia, truncal hypotonia, extremity hypertonia, seizures, and mental retardation though milder presentations exist. PCD has no symptoms other than transient alterations in tone. Treatment may include administration of BH4, L-dopa (and carbidopa) 5-hydroxytryptophan supplements, and a low phenylalanine diet.
Tyrosine is a nonessential amino acid that derives from dietary sources, the hydroxylation of phenylalanine, or protein breakdown. Primary (PKU) and secondary (defects of BH4 metabolism) hyperphenylalaninemia can cause abnormally low levels of tyrosine. Measurement of the phenylalanine:tyrosine ratio is helpful in monitoring appropriate dietary intake.
Monitoring effectiveness of dietary therapy in patients with hyperphenylalaninemia
The quantitative results of phenylalanine and tyrosine with age-dependent reference values are reported without added interpretation. When applicable, reports of abnormal results may contain an interpretation based on available clinical interpretation.
A phenylalanine:tyrosine ratio higher than 3 is considered abnormal.
The determination of plasma phenylalanine and tyrosine levels is not sufficient follow-up for abnormal newborn screening results, because other causes of hyperphenylalaninemia (eg, tetrahydrobiopterin deficiency) cannot be excluded by this test alone.
This test is not sufficient to establish a diagnosis of hyperphenylalaninemia.
Premature: 98-213 nmol/mL
0-31 days: 38-137 nmol/mL
1-24 months: 31-75 nmol/mL
2-18 years: 26-91 nmol/mL
> or =19 years: 35-85 nmol/mL
Result in mg/dL x 60.6=result in nmol/mL
Result in nmol/mL x 0.0165=result in mg/dL
Premature: 147-420 nmol/mL
0-31 days: 55-147 nmol/mL
1-24 months: 22-108 nmol/mL
2-18 years: 24-115 nmol/mL
> or =19 years: 34-112 nmol/mL
Result in mg/dL x 55.6=result in nmol/mL
Result in nmol/mL x 0.0181=result in mg/dL
See Inborn Errors of Amino Acid Metabolism in Special Instructions.
1. Mitchell GA, Grompe M, Lambert M, Tanguay RM: Hypertyrosinemia. In The Online Metabolic and Molecular Bases of Inherited Diseases. Edited by D Valle, AL BeaudetL, B Vogelstein, ET AL. New York, McGraw-Hill Medical, 2014. Accessed June 30, 2015. Available at http://ommbid.mhmedical.com/content.aspx?bookid=971&Sectionid=62673883
2. Donlon J, Sarkissian C, Levy H, Scriver CR: Hyperphenylalaninemia: Phenylalanine hydroxylase deficiency. In The Online Metabolic and Molecular Bases of Inherited Diseases. Edited by D Valle, AL Beaudet, B Vogelstein, et al. New York, McGraw-Hill Medical, 2014. Accessed June 30, 2015. Available at http://ommbid.mhmedical.com/content.aspx?bookid=971&Sectionid=62673211. Accessed June 30, 2015
3. Burgard P, Luo X, Hoffmann GF: Phenylketonuria. In Pediatric Endocrinology and Inborn Errors of Metabolism. Edited by K Sarafoglou, GF Hoffmann, KS Roth. New York, McGraw-Hill Medical Division, 2009, pp 163-168
4. Blau N, Thony B: Hyperphenylalanemias: Disorders of tetrahydrobiopterin metabolism. In Pediatric Endocrinology and Inborn Errors of Metabolism. Edited by K Sarafoglou, GF Hoffmann, KS Roth. New York, McGraw-Hill Medical Division, 2009, pp 169-175