Phenylketonuria

National Institutes of Health consensus development statement [1]National Institutes of Health Consensus Development Panel. National Institutes of Health consensus development conference statement: phenylketonuria - screening and management. 2000 [internet publication]. http://consensus.nih.gov/2000/2000Phenylketonuria113html.htm ​​

• Classical phenylketonuria (PKU): a disorder associated with high levels of blood phenylalanine (phe) (typically >1211 micromol/L [20 mg/dL]) and a complete absence or profound deficiency of phenylalanine hydroxylase (PAH) activity.[1]National Institutes of Health Consensus Development Panel. National Institutes of Health consensus development conference statement: phenylketonuria - screening and management. 2000 [internet publication]. http://consensus.nih.gov/2000/2000Phenylketonuria113html.htm ​​

• Non-PKU hyper-phenylalaninaemia: a lower elevation of blood phe.

• Exclusion of tetrahydrobiopterin (BH4) deficiency states is not specifically mentioned in definition but assumed.

European classification[2]Guldberg P, Rey F, Zschocke J, et al. A European multicenter study of phenylalanine hydroxylase deficiency: classification of 105 mutations and a general system for genotype-based prediction of metabolic phenotype. Am J Hum Genet. 1998;63:71-79. [Erratum in: Am J Hum Genet. 1998;63:1252-53.] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1377241/pdf/9634518.pdf http://www.ncbi.nlm.nih.gov/pubmed/9634518?tool=bestpractice.com

• Classical PKU: complete or near-complete deficiency of hepatic PAH activity accompanied in the patient by a dietary phe tolerance of <250-350 mg/day.

• Moderate PKU: characterised by a dietary phe tolerance of 350-400 mg/day.

• Mild PKU: characterised by a dietary phe tolerance of 400-600 mg/day.

• Mild hyper-phenylalaninaemia: a condition in which plasma phe levels are <605 micromol/L (10 mg/dL) on a normal diet.

Common practice in the US

• Classical PKU: blood phe on unrestricted diet >1211 micromol/L (20 mg/dL).

• Non-PKU hyper-phenylalaninaemia:

  • Mild-to-moderate or non-classical PKU: blood phe on unrestricted diet above the threshold for triggering intervention but <1211 micromol/L (20 mg/dL).

  • Benign hyper-phenylalaninaemia: blood phe on unrestricted diet above normal but below the threshold for triggering intervention (typically the threshold is 363 micromol/L [6 mg/dL]).

Patients who have hyper-phenylalaninaemia resulting from rare defects in tetrahydrobiopterin synthesis or recycling are excluded from this definition.