PHENYLKETONURIA

(PKU)
The normal metabolism of phenylalanine
(pathways a and b)

BREAKDOWN

Dietry
sources, PHENYLALANINE
particularly HYDROXYLASE
PHENYLALANINE TYROSINE
plant (a)
proteins

(b)
BODY
PROTEINS

© 2008 Paul Billiet ODWS

The abnormal metabolism in phenylketonuric subjects
(pathway c)

HYDROXYPHENYLACETIC
ACID

(c)
Dietry
sources, PHENYLALANINE
particularly HYDROXYLASE
PHENYLALANINE*
plant (a)
proteins
(c)
(b)
PHENYLACETIC BODY
ACID* PROTEINS

*Agents, thought to be responsible for mental retardation

© 2008 Paul Billiet ODWS
 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. 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

 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