Initial symptoms may include:
- a musty or "mousy" odor of the body and urine
- developmental delays in sitting, crawling, and standing
- decreased skin and hair pigmentation (due to lack of tyrosine)
- profound mental retardation
There are different forms of PKU defined by the highest levels of phenylalanine measured in blood. In benign hyperphenylalaninemia, the increase in phenylalanine levels are minimal (phenylalanine 120-360 micromolar, normal 30-90 micromolar) and require no treatment. In mild PKU, there is a mild increase in phenylalanine levels (360-1,200 micromolar, normal 30-90 micromolar) that is more easily controlled by diet or pharmacological therapy. In classic PKU, there is substantial elevation of phenylalanine levels (>1,200 micromolar, normal 30-90 micromolar) that requires strict dietary therapy and is less likely to respond to pharmacological therapy. Some patients, particularly those with mild PKU, respond to therapy with sapropterin, a synthetic form of tetrahydrobiopterin, the cofactor of phenylalanine hydroxylase. Patients with mild phenylketonuria are more likely to respond to this therapy.
Elevated phenylalanine levels can also be caused by defects in the synthesis or recycling of tetrahydrobiopterin, an essential cofactor of phenylalanine hydroxylase and other enzymes involved in neurotransmitter synthesis. These patients, in addition to elevated phenylalanine levels, can have neurotransmitter deficiencies and their treatment differs from that of phenylketonuria. As part of the initial evaluation of a child with high phenylalanine level in newborn screening, metabolic geneticists will exclude a defect in the tetrahydrobiopterin pathway by obtaining additional specialized tests. These consist of the measurement of pterin profile in urine spotted on filter paper and evaluation of the activity of an enzyme, di hydro pteridin reductase (DHPR), in red blood said spotted on filter paper. Therapy in these conditions include the administration of a synthetic form of tetrahydrobiopterin that can normalize plasma phenylalanine level. These patients also require the administration of neurotransmiter precursors.
Diet restriction needs to be continued for life in patients with PKU and repeated monitoring of plasma phenylalanine and tyrosine levels are needed to make sure that they remain within the therapeutic range (phenylalanine 45-360 micromolar, Tyrosine 30-120 micromolar).
Blau N, van Spronsen FJ, Levy HL.
Lancet. 2010;376(9750):1417-27. PubMed abstract
Viau KS, Wengreen HJ, Ernst SL, Cantor NL, Furtado LV, Longo N.
Correlation of age-specific phenylalanine levels with intellectual outcome in patients with phenylketonuria.
J Inherit Metab Dis. 2011. PubMed abstract
|Author:||Nicola Longo, MD, PhD - 8/2011|
|Compiled and edited by:||Lynne M Kerr, MD, PhD - 7/2011|
|Content Last Updated:||11/2011|
The authors listed above are responsible for the overall PKU and Pterin Defects Module. Authors contributing to individual pages in the module are listed on those pages.
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