Amino acid metabolism disorders like phenylketonuria, tyrosinemia and protein metabolism disorders along with classification of congenital anomlies

1. Classification of congenital
anomalies, disturbances of amino
acid metabolism and protein
metabolism
02-12-2017
Presented by
Aderao Ganesh N.
P-2063
Submitted to,
Dr. Narayan Dutta
Principal scientist

2. Congenital anomalies
 Can be defined as structural or functional
anomalies that occur during intrauterine
life (can be identified prenatally, at birth, or sometimes
may only be detected later in infancy, such as hearing
defects)
 Also known as
◦ Birth defects,
◦ Congenital disorders or congenital
malformations.
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3. Causes of 2.68 million deaths during the neonatal
period in 2015, worldwide
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(WHO, 2015)

4. Causes of congenital anomalies
 Genetic factors
◦ Inheritance of anomaly coding genes
◦ Mutations
 Socioeconomic and demographic factors
◦ lack of access to sufficient, nutritious foods and
poorer access to healthcare and screening for
pregnant
◦ Maternal age
 Environmental factors
◦ Maternal exposure to certain pesticides and
other chemicals, as well as certain medications,
alcohol, tobacco and radiation during pregnancy
 Infections
◦ Maternal infections such as syphilis and rubella
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5. Classification of the congenital
anomalies
 Primary anomalies
◦ abnormality in genetic composition that
will lead to defect in the structure of an
organ or a part of an organ
◦ source is internal factor
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6. Classification congenital anomalies
 Secondary anomalies
◦ Interruption or disruption of the normal
development of an organ due to external
factors like teratogenic agents e.g. infection,
chemical substance, ionizing radiation or a
trauma
◦ most widespread infectious agents are the
rubella virus, the cytomegaly virus and
toxoplasma gondii
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Phocomelia

7. Important to note
 Embryopathies (14-56 days)
 Foetopathies (56 days onwards)
 Congenital abnormality is not
necessarily to be inherited it can be
acquired during ontogenesis
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8. Disturbances of metabolism
 Due to defects in the breakdown of
amino acids or in the body’s ability to
get amino acids into cells
 Garrods hypothesis:
 A B X C
D (Toxic metabolite)
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9. Disturbances of metabolism
 An inherited enzyme deficiency
leading to the disruption of normal
bodily metabolism
◦ Accumulation of a toxic substrate
(compound acted upon by an enzyme in a
chemical reaction)
◦ Impaired formation of a product
normally ̔produced by the deficient
enzyme
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10. Types of amino acid metabolism
disorders
 PHENYLKETONURIA
 MAPLE SYRUP URINE DISEASE
 HOMOCYSTINURIA
 TYROSINEMIA
 ALCAPTONURIA
 GLYCINURIA
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11. PHENYLKETONURIA
 Due to lack of the enzyme Phenylalanine
hydroxylase.
 Phenylalanine hydroxylase required for
conversion of phenylalanine to tyrosine.
 Phenylanine accumulate in blood and reaches
to brain, toxic to brain (in excess conc.)
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(Guthrine and Susi 1963).

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13. PHENYLKETONURIA
 Nervous symptoms are observed e.g.
Seizures, aggressive or self-injurious
behavior, hyperactivity and intellectual
disability.
 Treatment:
◦ Restrict phenylalanine intake
◦ Restrict meat, milk, or other common foods
that contain protein
◦ Special nutritional products, including infant
formula without phenylalanine, are also
available that should be fed.
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14. MAPLE SYRUP URINE DISEASE
 Maple syrup urine disease (MSUD) is
caused by lack of the branched-
chain alpha-ketoacid
dehydrogenase complex (BCKAD)
enzymes
(Mackenzie and Woolf, 1959; Dancis et al.,
1959).
 These enzymes are responsible for
breaking down the branched chain
amino acids i.e. leucine, isoleucine,
and valine that are in protein-rich02-12-2017

15. MAPLE SYRUP URINE DISEASE
 Accumulation of these amino acids and their
toxic by-products (ketoacids) results in the
serious health problems associated with
MSUD
 Excretion of these compounds also impart
maple syrup smell to sweat and other body
secretions
 Causes
◦ neurologic changes,
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16. HOMOCYSTINURIA
 Caused by lack of the enzyme
cystathionine beta synthase - needed
to metabolize homocysteine
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(Mudd et al., 1964, Mudd et al., 1985).

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18. HOMOCYSTINURIA
 Symptoms
◦ Decreased vision and
◦ Skeletal abnormalities
◦ Spontaneously blood clotting resulting in
strokes
◦ High blood pressure
 Treatment and control measures
◦ Improved when given vitamin B6
(pyridoxine) or vitamin B12 (cobalamin)
(Wilcken et al.,
1997)
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19. TYROSINEMIA
 Caused by lack of the enzyme –
4-hydroxyphenylpyruvate
dioxygenase
 Mostly affects the liver and the
kidneys
02-12-2017(Lindblad et al., 1977; Kvittingen, 1986)

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21. TYROSINEMIA
 Types of Tyrosinemia
◦ Type I (most common)
◦ Type II
 Symptoms
◦ Type I - dysfunction of the liver, kidneys, and
nerves, resulting in irritability, rickets, or even
liver failure and death
◦ Restriction of tyrosine is of little help
◦ Type II -intellectual disability and frequently
develop sores on the skin and eyes.
◦ Restriction of tyrosine in the diet can prevent
problems from developing.
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22. Disturbances of protein metabolism
 Defective Proteins and Disease
◦ Oxygen carrying proteins
◦ Connective tissue proteins
◦ Clotting factors
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23. OXYGEN CARRYING PROTEINS
 Sickle-Cell Anemia
 B-Talassemia
 A-Talassemia
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24. CONNECTIVE TISSUE PROTEINS
 Occipital Horn Syndrome Cutis Laxa,
X-linked
 Osteogenesis Imperfecta Type I
 Osteogenesis Imperfecta Type I-C
 Osteogenesis Imperfecta Silent Type
II/III
 Osteogenesis Imperfecta Type IV
 Osteogenesis Imperfecta Neonatal
Lethal form
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25. CLOTTING FACTORS
 Afibrinogenemia complete loss of fibrinogen, Factor I
 Dysfibrinogenemia dysfunctional fibrinogen, Factor I
 Factor II Disorders
 Factor III (tissue factor) is the only coagulation factor for
which a congenital defect has not been identified
 Factor V Deficiency Labile Factor deficiency
 Factor VII Deficiency
 Hemophilia A Factor VIII deficiency
 Hemophilia B Factor IX deficiency
 Factor X Deficiency
 Factor XI Deficiency Rosenthal Syndrome, Plasma
Thromboplastin Antecedent (PTA) deficiency
 Factor XII Deficiency Hageman factor deficiency
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26. Conclusion
 Most of the disturbances in
metabolism are caused due to point
mutation in genes coding for the
enzymes
 Theses disturbances can be treated
by restricting the diet with the toxic
compound
 Also, can be prevented by avoiding
inbreeding of diagnosed individuals.
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