Disorder of phenylalanine hydroxylation leading to accumulation of this amino acid.
Patients with undiagnosed PKU have progressive developmental delay in the
first year of life, severe mental retardation, seizures, autistic-like behavior and a peculiar odor.
Bacterial inhibition assay to measure blood phenylalanine
Using a cut-off level of 4 mg/dL, miss 16% under 24 hours, 2% over 48 hours old
Guthrie bacterial inhibition test
: the prototype of metabolic screening tests relying on bacterial inhibition. Filter paper is saturated with heel-stick blood, allowed
to dry, small disks are punched out for use in tests. Bacillus subtilis is spread uniformly on agar. Inhibitory amino acid analogs block specific metabolic pathways.
Bacterial can grow only if exogenous amino acids competitively overcome the block. Can test in this manner for phenylalanine, leucine, methionine, galastosemia,
histidine, and tyrosine. Antibiotics can also inhibit growth, however, causing false negatives.
False positives (1-3% of cases)
non-PKU hyperphenylalanemia (1/60,000)
pterin defect with secondarily hyperphenylalanemia
transient elevation, acute galatosemia
incorrect age, s/p transfusion
urine screening unreliable in infants
1:10,000 to 1:25,000 in US
1:6,000 in Ireland, Scotland and among the Yemenite Jews
Frequently seen with biopterin and dihydropteridine reductase deficiencies
DNA mutation heterogenous
Most commonly causes by a deficiency of phenylalanine hydroxylase leading to an accumulation of phenylalanine, which impairs the development of the central
Rarely diagnosed before 6 months and usually only after mental retardation is obvious
Paler and fairer than siblings because melanin formation is competitively inhibited by high phenylalanine levels
Progressive developmental delay in the first year of life, severe mental retardation, seizures, autistic-like behavior and a peculiar odor. Hyperactivity and eczema
Dietary restriction of phenylalanine is highly effective if begun before the infant is 4 weeks old. Diet requires protein restriction and avoidanace of aspartame.