1. PHENYLKETONURIA (PKU)
© 2016 Paul Billiet ODWS

2. PHENYLALANINE HYDROXYLASE
The normal metabolism of phenylalanine
(pathways a and b)
BREAKDOWN
Dietry sources, particularly plant proteins
PHENYLALANINE HYDROXYLASE
PHENYLALANINE
TYROSINE
(b)
(a)
BODY PROTEINS
© 2016 Paul Billiet ODWS

3. PHENYLALANINE HYDROXYLASE
The abnormal metabolism in phenylketonuric subjects
(pathway c)
HYDROXYPHENYLACETIC ACID
(c)
PHENYLALANINE*
Dietry sources, particularly plant proteins
BODY PROTEINS
(b)
(a)
PHENYLALANINE HYDROXYLASE
(c)
PHENYLACETIC ACID*
*Agents, thought to be responsible for mental retardation
© 2016 Paul Billiet ODWS

4. Test
Ferric chloride + urine of new born baby Green colour in the presence of ketone bodies
© 2016 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
© 2016 Paul Billiet ODWS

6. Frequency 1 in 10 000 in Caucasians of NW Europe
© 2016 Paul Billiet ODWS

7. Causes
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
© 2016 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
© 2016 Paul Billiet ODWS