PHENYLKETONURIA PKU 2016 Paul Billiet ODWS The normal
PHENYLKETONURIA (PKU) © 2016 Paul Billiet ODWS
The normal metabolism of phenylalanine (pathways a and b) BREAKDOWN Dietry sources, particularly plant proteins PHENYLALANINE HYDROXYLASE (a) TYROSINE (b) BODY PROTEINS © 2016 Paul Billiet ODWS
The abnormal metabolism in phenylketonuric subjects (pathway c) HYDROXYPHENYLACETIC ACID Dietry sources, particularly plant proteins (c) PHENYLALANINE* PHENYLALANINE HYDROXYLASE (a) (c) (b) PHENYLACETIC ACID* *Agents, thought to be responsible for mental retardation BODY PROTEINS © 2016 Paul Billiet ODWS
Test p Ferric chloride + urine of new born baby Green colour in the presence of ketone bodies © 2016 Paul Billiet ODWS
Treatment A strictly controlled phenylalanine free diet p up to the age of about 14 years old p phenylalanine is itself an essential amino acid small doses must be supplied p After this age the growth and development of the brain is not affected by high levels of phenylalanine in the body p © 2016 Paul Billiet ODWS
Frequency p 1 in 10 000 in Caucasians of NW Europe © 2016 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 © 2016 Paul Billiet ODWS
Evolution Heterozygotes (carriers) are thought to be less susceptible to toxins produced by the moulds Aspergillus and Penecillium p These grow on foods in damp wet climates (e. g. NW Europe) p Heterozygous women show lower spontaneous abortion rates p © 2016 Paul Billiet ODWS
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