Phenylketonuria (PKU) is a genetic disorder caused by mutations affecting the metabolism of phenylalanine, leading to severe neurological effects such as mental retardation and seizures. Diagnosis involves increased serum phenylalanine levels, and treatment typically includes a low-protein diet, while future therapies may involve gene and stem cell treatments. PKU also results in characteristic symptoms like hypopigmentation and a distinctive mousy odor of urine due to metabolite excretion.

1. Phenylketonuria
Dr Rohini C Sane

2. Metabolism of Phenyl alanine & Tyrosine
• phenyl alanine -essential
• Tyrosine- non essential
• Phenyl alanine & Tyrosine- Glucogenic & Ketogenic

3. Metabolism of Phenyl alanine & Tyrosine

4. Ketogenic
Glucogenic
Metabolism of
Phenylalanine
& Tyrosine

6. Causes OF Phenylalanine
1.Genetic Mutation of Phenylalanine 2. Genetic Mutation of Dihydropterin Reductase

8. Phenylketonuria
& Mental Retardation

9. Phenylketonuria & Central Nervous system
• Autosomal recessive gene
Effects on central nervous system
1. Mental retardation
2. Failure to walk or talk
3. Failure of growth
4. Seizure
5. Tremers
6. Low IQ

10. Phenylketonuria & Serotonin
• Accumulation of Phenylalanine in brain impairs transport &
metabolism of tryptophan& Tyrosine
• Synthesis of Serotonin decreased  defective synthesis of myelin
sheath
• Tryptophan
↓
Serotonin ( an excitatory neurotransmitter from Tryptophan)

11. Inheritance of
Phenylketonuria

12. Of Phenylketonuria

13. Phenylketonuria-
& Chromosome 12

14. Phenylketonuria

15. Phenylketonuria-defective hormone synthesis

16. Phenylketonuria-defective Hormone synthesis

17. Hypopigmentation -Lack of pigmentation in skin ,eyes , hair
Decrease melanin synthesis from Tyrosine ( phenylalanine is substrate for
synthesis )

18. Phenylketonuria-
Mousy Odour of
urine

19.  Elevated levels of
Phenylalanine
Phenyl lactate MOUSY ODOR OF URINE
Phenyl acetate
Phenyl glutamine
Phenylketonuria- Urinary excretion of metabolites

20. Phenylketonuria-
Urinary excretion of metabolites

26. Diagnosis of Phenylketonuria
• Increased serum levels of Phenylalanine
• Guthrie test (BIOASSAY -USING BACILLUS SUBTILIS )
• URINE + FeCl3  GREEN COLOR

27. Diagnosis of Phenylketonuria

28. Diagnosis of Phenylketonuria-Guthrie test

29. Diagnosis of Phenylketonuria

30. Diagnosis of Phenylketonuria

31. Treatment of Phenylketonuria - (Dietary )
1. Low protein diet
2. Low Phe contents for 5 yrs
3. 5- hydroxy TRP/DOPA supplementation 
synthesis of Dopa /serotinine /catecholamines
4. Supplementation of Tyrosine

33. Treatment of Phenylketonuria –(Genetic)
Treatment of Phenylketonuria-awaited for clinical trials
• Gene Therapy
• Stem cell therapy

34. Treatment of Phenylketonuria-Gene therapy

35. Treatment of Phenylketonuria-Ex –vivo Gene therapy

36. Treatment of Phenylketonuria –Stem cell therapy