PKUtype

PKUtype is a term used in genetic and metabolic medicine to describe the spectrum of phenotypes associated with phenylketonuria (PKU). It refers to a way of categorizing PKU presentations based on residual activity of the enzyme phenylalanine hydroxylase (PAH) and, in some cases, responsiveness to treatment such as tetrahydrobiopterin (BH4). PKUtype is descriptive rather than a separate diagnostic category and is used to guide prognosis and management in addition to standard diagnostic criteria.

Classification and examples: Classic PKU denotes near-complete or complete PAH deficiency with persistently high phenylalanine levels from birth, typically requiring strict lifelong dietary restriction of phenylalanine. Mild PKU or mild hyperphenylalaninemia describes higher but less extreme phenylalanine elevations and may be managed with a more liberal diet or targeted therapy. BH4-responsive PKU refers to individuals whose PAH activity can be enhanced with BH4, allowing partial dietary relaxation and use of BH4 as an adjunct therapy. Some centers further subsume variant presentations under PKUtype based on specific PAH mutations, which can inform predicted severity and response to therapy.

Genetic basis and testing: PKUtype often corresponds to PAH gene variants. Genetic testing can identify mutation classes, such as null, missense, or splice-site mutations, and newborn screening results provide early phenylalanine measurements used in conjunction with PKUtype labeling.

Clinical implications: PKUtype can aid counseling by indicating expected metabolic control, dietary needs, and potential BH4 responsiveness. It should not replace established diagnostic criteria or comprehensive genotype-phenotype assessment, and terminology may vary between institutions.

See also: Phenylketonuria, PAH gene, BH4, newborn screening.