in this presentation, u will get to know about the causes of enzyme deficiency and how we can treat it

1. ENZYME DEFICIENCY AND
ITS TREATMENT
BY- ROBIN SINGH
B.SC (HONS) BIOCHEMISTRY

2. What is enzyme deficiency
 Enzyme deficiencies, or the absence of
these enzymes, are inherited defects that result in a
number of life-changing or life-threatening
conditions: MPS: The mucopolysaccharidoses are a
group of inherited diseases in which a defective or
missing enzyme causes complex sugar molecules to
accumulate in cells.

3. Enzyme deficiency effect
 Enzymes are special types of proteins required to break down food
molecules into fuel during metabolism, the process by which the
body gets energy for normal growth and development. Enzyme
deficiencies, or the absence of these enzymes, are inherited defects
that result in a number of life-changing or life-threatening
conditions:
 MPS:
 The mucopolysaccharidoses are a group of inherited diseases in
which a defective or missing enzyme causes complex sugar
molecules to accumulate in cells. As a result, progressive damage is
done to the heart, bones, joints, respiratory system and central
nervous system. While the disease may not be apparent at birth,
signs and symptoms develop with age as more cells become
damaged. It is estimated that one in every 25,000 babies born in the
United States has some form of MPS.

4. Orotic acidurea
 Orotic aciduria (AKA hereditary orotic aciduria) is a
disease caused by an enzyme deficiency resulting in
a decreased ability to synthesize pyrimidines. It is
the only known enzyme deficiency of the de
novo pyrimidines synthesis pathway.
 Orotic aciduria is characterized by excessive
excretion of orotic acid in urine because of the
inability to convert orotic acid to UMP. It causes
megaloblastic anemia and may be associated with
mental and physical developmental delays

5. Signs and symptoms
 Patients typically present with excessive orotic acid
in the urine, failure to thrive, developmental delay,
and megaloblastic anemia which cannot be cured by
administration of vitamin B12 or folic acid.

6. Cause and genetics
 Orotic aciduria has an autosomal recessive mode of
inheritance.
 This autosomal recessive disorder is caused by a deficiency in
the enzyme UMPS, a bifunctional protein that includes the
enzyme activities of OPRT and ODC. In one study of three
patients, UMPS activity ranged from 2-7% of normal levels.
 Two types of orotic aciduria have been reported. Type I has a
severe deficiency of both activities of UMP synthase. In Type
II orotic aciduria, the ODC activity is deficient while OPRT
activity is elevated. As of 1988, only one case of type II orotic
aciduria had ever been reported.
 Orotic aciduria is associated with megaloblastic anemia due to
decreased pyrimidine synthesis, which leads to decreased
nucleotide-lipid cofactors needed for erythrocyte membrane
synthesis in the bone marrow.

8. Diagnosis
 Elevated urinary orotic acid levels can also arise
secondary to blockage of the urea cycle, particularly
in ornithine transcarbamylase deficiency (OTC
deficiency). This can be distinguished from hereditary
orotic aciduria by assessing blood ammonia levels
and blood urea nitrogen (BUN). In OTC
deficiency, hyperammonemia and decreased BUN are
seen because the urea cycle is not functioning properly,
but megaloblastic anemia will not occur because
pyrimidine synthesis is not affected.[7] In orotic aciduria,
the urea cycle is not affected.
 Orotic aciduria can be diagnosed through genetic
sequencing of the UMPS gene

9. Treatment
 Treatment is administration of uridine
monophosphate (UMP) or uridine triacetate (which
is converted to UMP). These medications will bypass
the missing enzyme and provide the body with a
source of pyrimidines.

10. THANK YOU
End