This presentation is about the a disease , causes and cure. Also it contains the experiments done on mouse models.I tried to explain it with the help of cathy diagrams.

1. PHENYLKETONURIA(
PKU)
By-SHIVANSHI SONI
E20BIO014

2. • Phenylketonuria (PKU), less commonly known as
phenylalanine hydroxylase(PAH) deficiency.
• The most common inborn error of amino acid metabolism.
• It is an autosomal recessive metabolic genetic disorder.
• Phenylalanine is an essential amino acid.

4. GENETICS OF PKU
• Two people who conceive a child must both be the
carriers of the defective gene in order for their child
to have the disorder.
• The “carrier” for PKU does not have the symptoms

5. • The enzyme for pku is present on long arm of chromosome
number12
• More than 500 different mutations in the PAH gene have been
identified.
• PKU is caused by a mutational defect in the gene that helps to
create the enzyme needed for break down of phenylalanine.

6. DIAGNOSIS
• Diagnosis is done through screening test in immediate post
natal period.
• Guthrie test is a screening for PKU used to detect abnormal
phe metabolites in the blood.
• Prenatal diagnosis can be accomplished by DNA
mutation analysis following amniocentesis.

7. SYMPTOMS

8. TITLE LOREM IPSUM DOLOR

9. STATISTICS OF OCCURRENCE

10. • No Meat
• No dry beans
• No nuts
• No eggs
• No dairy products
Prevention and Treatment

11. THERE IS NO CURE FOR PKU, BUT
TREATMENT CAN PREVENT
INTELLECTUAL DISABILITIES AND
OTHER HEALTH PROBLEMS.

12. • A dangerous buildup of phenylalanine can develop when a
person with PKU eats protein-rich foods or eats aspartame, an
artificial sweetener.
• This buildup of phenylalanine results in damage to nerve cells in
the brain

13. GENE THERAPY
• gene therapy designed to normalize blood phenylalanine (Phe)
concentration levels in patients with PKU by inserting a correct
copy of the PAH gene into liver cells.
• Certain viruses are often used as vectors because they can
deliver the new gene by infecting the cell.
• The vector can be injected or given intravenously directly into a
specific tissue in the body, where it is taken up by individual
cells.

14. GENE THERAPY

15. MEDICATION
• The goal of PKU treatment is to maintain the blood level of
phenylalanine between 2 and 10 mg/dl.
• The Food and Drug Administration (FDA) has approved the drug
sapropterin (Kuvan) for the treatment of PKU. It works by
increasing your tolerance to phenylalanine. The drug is for use
in combination with a PKU diet.
• Sapropterin is a synthetic form of BH4, the cofactor for the
enzyme PAH.

16. TYPES OF PKU
There are four types of PKU:
• Hyperphenylalaninemia:-the lowest level above normal.
• Mutations in PAH will result in a phenotypically mild form of PKU
called hyperphenylalanemia
• Mild PKU: blood levels are mildly elevated.
• Moderate or variant: levels are not low but not high.
Classic PKU:-Most appear normal at birth.
• blood levels of phenylanine are high
• It is caused by mutations in both alleles of the gene for
phenylalanine hydroxylase (PAH), found on chromosome 12

17. DIFFERENCE BETWEEN DIFFERENT TYPES

18. MATERNAL AND MALIGNANT PKU
Maternal PKU :-
• Untreated PKU during pregnancy can result in maternal PKU syndrome
• It is a genetic inborn error and mother has Hyperphenylalaninemia.
• Malignant PKU:-
• DHPR deficiency is a rare autosomal recessively inherited
metabolic disorder of tetrahydrobiopterin (BH4) regeneration.
• Clinical symptoms may comprise microcephaly, developmental
delay, ataxia and seizures.

19. KNOCKOUT MOUSE TEST
• The mouse model of PKU mimics the PKU patients through a chemically
induced point mutation in the gene encoding for the enzyme PAH
• No adverse effect was observed during the trials.
• They combined mouse germline(sex cells) mutations with screens for
hyperphenylalaninemia to isolate three mutants deficient in phenylalanine
hydroxylase (PAH) activity and cross-reactive protein(CRP).
• Two of these have reduced PAH mRNA and display characteristics
of untreated human PKU patients.
• A low PHE diet partially reverses these abnormalities

20. PHENOTYPE OF KNOCKOUT MOUSE TEST

21. PKU : A CASE STUDY
• A 2 month pregnant, 20 year old female.
• Mild to moderate PKU.
• Diagnosed with PKU shortly after birth (700 umol/L) and was
immediately placed on a Phe-restricted medical diet.
• Blood Phe relatively stable during course of pregnancy.
• 7 months later, a male infant, with expected size and weight, normal
Phe levels and no obvious birth defects, was delivered.
• Genetic testing showed that he had heterozygosity of the PAH gene
with one normal allele.

22. THANK YOU!