3. PHENILKETONURIA(PKU)
• Deficiency of phenylalanine hydroxylase or
a defect in biosynthesis/reduction of
tetrahidrobiopterin
• Urinary excretion of phenlypruvate and
phenyllactate
• Defective neural development
• Severe mental retardation
• Very light skin pigmentation
3
4. • Unusual gait, stance, sitting posture
• High frequency of epilepsy
• Autosomal recessive
• Phenylalanine hydroxylase :Mixed function
oxidase that uses cofactor
(tetrahydrobiopterin ) and molecular
oxygen
4
5. • Therapy:Diet restricted in phenylalanine but
• supplemented with tyrosine
• Don't consume protein-rich foods
• Natural proteins, such as casein of milk, must be
first hydrolyzed and phenylalanine removed
• Foods sweetened with aspartame should be
avoided
• . 5
6. • In patients with PKU,
• Phenylalanine undergoes transaminaton
with pyruvate to yield phenyl pyruvate.
• Phenylpyruvate is either decarboxylated to
phenylacetate or reduced to phenylactate.
• Phenylacetate imports a characteristic
odor to urine.
6
7. • When there is a defect in the enzyme that
catalyzes the regeneration of
tetrahydrobiopterin, diet must be supplemented
with L-dopa and 5-hydroxytryptophan
(precursors of neurotransmitters norepinephrine
and serotonin respectively)
• Supplementing diet with tetrahydrobiopterin is
ineffective because it is unstable and does not
cross the blood-brain barrier.
7
8. • ALBİNİSM
• Lack of tyrosinase
• A marked lack of pigmentation
• Sensitive to damage from sunlight and
must take added precaution against UV
radiation
• Normal eyesight
• No neurologic deficits.
8
9. • Tyrosine hydroxylase and aromatic amino
acid decarboxylase deficiencies:Inherited
causes of impaired biogenic amine
metabolism
9
11. • Inherited disorder affecting the activity of
tyrosine hydroxylase results in brain dopamine
deficiency.
• Progressive gait disorder and infantile
parkinsonism
• Treatment: L-Dopa administration
• To prevent decarboxylation of L-Dopa to
dopamine in the blood by peripheric
AADC,(aromatic amino acid decarbooxylase) an
inhibitor ,which does not affect brain AADC
activity ,is given together with L-Dopa.
11
12. • Such inhibition optimizes the transport of
L-Dopa across the blood-brain barrier.
• Within the brain AADC can convert L-
Dopa to Dopamine
• AADC also catalyzes the conversion of 5-
0H tryptophan to serotonin
• Inborn error affecting AADC activity
results in brain deficiency of both
dopamine and serotonin.
12
13. • Severe movement disorder +abnormal eye
movement +neurologic impairment.
• Treatment:Monoamino oxidase inhibitors
dopamine agonists (pergoliode
bromocryptine)
13
14. • ALKAPTONURİA (Black urine disease)
• Lack of homogentisate oxidase
• Homogentisic acid accumulates and is
excreted in the urine.
• This compound oxidizes on standing or on
treatment with alkali, gives the urine a
dark color
14
16. • Deposition of dark (ochre-colored)pigment
in cartilage tissue
severe arthritis
connective tissue pigmentation(ochronis)
16
17. • autosomal recessive
• symptoms start in 3 rd/4 th decade
• relatively benign in comparison to PKU
17
18. Maple Syrup Urine Disease
(MSUD )
Defect in branched-chain α keto acid
dehydrogenase, a multienzyme complex
associated with inner membrance of
mitochondrion
Branched chain ketonuria
18
19. • Accumulation of-keto acids and hydroxy
acids (especially leucine ) in blood and
urine.
• Physical and mental retardation of new
born
• Distinct maple syrup odor
19
20. • Therapy:
• Low-protein or modified diet
• Supplementation of high doses of thiamine
pyrophosphate
• Limit the intake of valine, leucine,
isoleucine.
20
