PhenylketonuriaDr Rohini C Sane

Metabolism of Phenyl alanine & Tyrosine• phenyl alanine -essential

• Tyrosine- non essential

• Phenyl alanine & Tyrosine- Glucogenic & Ketogenic

Metabolism of Phenyl alanine & Tyrosine

KetogenicGlucogenic

Metabolism ofPhenylalanine & Tyrosine

Causes OF Phenylalanine1.Genetic Mutation of Phenylalanine 2. Genetic Mutation of Dihydropterin Reductase

Phenylketonuria & Mental Retardation

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

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)

Inheritance ofPhenylketonuria

Of Phenylketonuria

Phenylketonuria-

& Chromosome 12

Phenylketonuria

Phenylketonuria-defective hormone synthesis

Phenylketonuria-defective Hormone synthesis

Hypopigmentation -Lack of pigmentation in skin ,eyes , hairDecrease melanin synthesis from Tyrosine ( phenylalanine is substrate for synthesis )

Phenylketonuria-Mousy Odour of

urine

Elevated levels of Phenylalanine Phenyl lactate MOUSY ODOR OF URINEPhenyl acetate Phenyl glutamine

Phenylketonuria- Urinary excretion of metabolites

Phenylketonuria-Urinary excretion of metabolites

Diagnosis of Phenylketonuria• Increased serum levels of Phenylalanine

• Guthrie test (BIOASSAY -USING BACILLUS SUBTILIS )

• URINE + FeCl3 GREEN COLOR

Diagnosis of Phenylketonuria

Diagnosis of Phenylketonuria-Guthrie test

Diagnosis of Phenylketonuria

Diagnosis of Phenylketonuria

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

Treatment of Phenylketonuria –(Genetic)

Treatment of Phenylketonuria-awaited for clinical trials

• Gene Therapy

• Stem cell therapy

Treatment of Phenylketonuria-Gene therapy

Treatment of Phenylketonuria-Ex –vivo Gene therapy

Treatment of Phenylketonuria –Stem cell therapy