1. PHENYLKETONURIA
(PKU)

2. PHENYLALANINE
HYDROXYLASE
PHENYLALANINE
Dietry
sources,
particularly
plant
proteins
BODY
PROTEINS
BREAKDOWN
(b)
(a)
The normal metabolism of phenylalanine
(pathways a and b)
TYROSINE
© 2008 Paul Billiet ODWS

3. HYDROXYPHENYLACETIC
ACID
PHENYLACETIC
ACID*
(c)
(c)
The abnormal metabolism in phenylketonuric subjects
(pathway c)
*Agents, thought to be responsible for mental retardation
PHENYLALANINE*
Dietry
sources,
particularly
plant
proteins
BODY
PROTEINS
(b)
(a)
PHENYLALANINE
HYDROXYLASE
© 2008 Paul Billiet ODWS

4. Test
 Ferric chloride + urine of new born baby→
Green colour in the presence of ketone
bodies
© 2008 Paul Billiet ODWS

5. 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

6. Frequency
 1 in 10 000 in Caucasians of NW Europe
© 2008 Paul Billiet ODWS

7. Causes
1. A single mutant recessive allele of the
Phenylalanine Hydroxylase (PAH) gene
Locus : Long arm of Chromosome 12
2. Dietary excess of plant proteins which
results in the exhaustion of a protein
cofactor (pterin) needed by the enzyme
© 2008 Paul Billiet ODWS

8. 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