Phenylketonuria

Description

Phenylketonuria (PKU) is caused by a complete (or near-complete) deficiency of phenylaline hydroxylase (PAH). Untreated children with a deficiency of PAH can develop profound and irreversible mental retardation. Early diagnosis is important as the mental retardation can be prevented with dietary modifications. Disorders of PAH cause a spectrum of disease, PKU, variant PKU, and non-PHU hyperphenylalaninemia. Each type has different risk of the level of cognitive impairment. The deficiency of PAH causes inability to breakdown phenylaline (phe) and the subsequent build-up of phenylaline and its metabolites in the plasma. The elevated plasma levels have effects on brain development.

Genetics

• Autosomal recessive:
• PAH gene at 12q22-q24 chromosomal locus
• > 380 disease-causing mutations identified.

Testing

• Newborn screening detects virtually 100% of cases. (Guthrie card bloodspot).
• PKU characterized by plasma phenylalanine concentrations above 1000 µmol/l.
• Molecular genetic testing available for carrier status. Two types: mutation analysis and linkage analysis.
• Tandem mass spectrometry - increased accuracy.

References

1. OMIM ID 261600
2. Locus Link: 5053
   
3. Gene Clinics: Phenylalanine Hydroxylase Deficiency