PHENYLKETONURIA
(PKU)
The normal metabolism of phenylalanine
(pathways a and b)
BREAKDOWN
Dietry
sources,
particularly
plant
proteins
PHENYLALANINE
PHENYLALANINE
HYDROXYLASE
(a)
TYROSINE
(b)
BODY
PROTEINS
© 2008 Paul Billiet ODWS
The abnormal metabolism in phenylketonuric subjects
(pathway c)
HYDROXYPHENYLACETIC
ACID
Dietry
sources,
particularly
plant
proteins
(c)
PHENYLALANINE
HYDROXYLASE
PHENYLALANINE*
(a)
(c)
(b)
PHENYLACETIC
ACID*
*Agents, thought to be responsible for mental retardation
© 2008 Paul Billiet ODWS
BODY
PROTEINS
Test

Ferric chloride + urine of new born baby
Green colour in the presence of ketone
bodies
© 2008 Paul Billiet ODWS
Treatment
A strictly controlled phenylalanine free diet
 up to the age of about 14 years old
 phenylalanine is itself an essential amino
acid small doses must be supplied
 After this age the growth and
development of the brain is not affected
by high levels of phenylalanine in the body

© 2008 Paul Billiet ODWS
Frequency

1 in 10 000 in Caucasians of NW Europe
© 2008 Paul Billiet ODWS
Causes
1.
2.
A single mutant recessive allele of the
Phenylalanine Hydroxylase (PAH) gene
Locus : Long arm of Chromosome 12
Dietary excess of plant proteins which
results in the exhaustion of a protein
cofactor (pterin) needed by the enzyme
© 2008 Paul Billiet ODWS
Evolution
Heterozygotes (carriers) are thought to be
less susceptible to toxins produced by the
moulds Aspergillus and Penecillium
 These grow on foods in damp wet climates
(e.g. NW Europe)
 Heterozygous women show lower
spontaneous abortion rates

© 2008 Paul Billiet ODWS