phenylketonuria (PKU)

Pathology

• hyperphenylalaninemia

Genetics

• autosomal recessive form associated with defects in PAH
• associated with defects in DBT gene
• severe atypical form associated with defects in GCH1 gene

Clinical manifestations

• progressive neurologic illness
• mental retardation
• severe muscular hypotonia
• light pigmentation
• rashes similar to eczema
• epilepsy
• unpleasant 'mousy' odor

• mood disorder*
• hyperactivity/inattention*
• executive dysfunction*
• impulsivity*
• psychotic states*

* manifestations of non-compliance with low phenylalanine diet

Laboratory

• phenylalanine in dried blood spot (screening)
• phenylalanine in blood
  • concentrations of phenylalanine persistently > 1200 pM (normal concentration 100 pM)
• PAH gene mutation

Management

• low phenylalanine diet is introduced early in life
• sapropterin (Kuvan) may help some patients
• a vegetarian diet or a diet that restricts animal proteins is insufficient for control of phenylketonuria

More general terms

• metabolic brain disease
• amino acid inborn error of metabolism

More specific terms

• phenylketonuria 2 (dihydropteridine reductase deficiency)

Additional terms

• hyperphenylalaninemia
• PAH gene mutation; phenylalanine hydroxylase gene mutation; phenylketonuria genotyping
• screening for phenylketonuria

Database

• OMIM: https://mirror.omim.org/entry/261600