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Discussion Starter · #1 ·
A 3 year old Caucasian boy is brought by his parents to the clinic because they think he looks "pale" and "weak". On examination the boy is lethargic and has pale conjunctivae. Blood analysis denotes megaloblastic anemia. Urine analysis shows excess carbamoyl phosphate derivative in the urine. There are no other abnormalities. The most likely cause for this boy's condition is:

A. Vitamin B12 deficiency
B. Folic acid excess
C. Ornithine transcarbamoylase deficiency
D. Orotidine 5'-phosphate decarboxylase deficiency
E. Carbamoyl phosphate synthetase I deficiency

Please attach an explanation to your answer.
 

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D. Orotidine 5'-phosphate decarboxylase deficiency....:D
it causes megaloblastic anemia that is resistant to Vit B12 ,folic acid or iron....
 

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I think it's D.

The other's are wrong because:

A = You should have increased methylmalonic acid in urine.
B = You could have folic acid excess without B12 deficiency and even then the above would be seen in urine.
C = OTC def would have orotic acid (a CP derivative) in urine, but would also be associated with symptoms of hyperammonemia (convulsions, coma, etc.). My only question here would be if "weak" i.e. lethargy would qualify as an early sign of hyperammonemia.
E = CPS 1 def is wrong because there's no orotic aciduria associated with it.
 

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D?

Orotidine decarboxylase is required for the UMP synthesis, lack of which blocks pyrimidine (DNA) synthesis leading to Megaloblastic Anemia.

CPS 1 is a urea cycle enzyme in the Mitochondria...others do not make any sense...
 

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Discussion Starter · #5 ·
You got it easily this time it seems! :D
Very good!

Correct answer is:
D. Orotidine 5'-phosphate decarboxylase deficiency

dazzles's explanation is very accurate, so I'll quote it:

A = You should have increased methylmalonic acid in urine.
B = You could have folic acid excess without B12 deficiency and even then the above would be seen in urine.
C = OTC def would have orotic acid (a CP derivative) in urine, but would also be associated with symptoms of hyperammonemia (convulsions, coma, etc.).
E = CPS 1 def is wrong because there's no orotic aciduria associated with it.
By the way, also a deficiency of orotic acid phosphoribosyltransferase would cause the same condition. Both this, and orotodine 5'-phosphate decarboxylase catalyze the formation of UMP from orotic acid in the de novo pyrimidine synthesis.

Also note that there's no hyperammonemia here because urea cycle enzymes are OK. On the other hand, a deficinecy of ornithine transcarbamoylase halts the urea cycle, so hyperammonemia ensues.
 

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Where exactly is this enzyme located in the pyrimidine synthesis pathway? Can someone present a diagram? I am using the Kaplan notes and this part is not very well explained. Thanks!
 

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Where exactly is this enzyme located in the pyrimidine synthesis pathway? Can someone present a diagram? I am using the Kaplan notes and this part is not very well explained. Thanks!
If you have FA, please refer to the Molecular Biochemistry part of Purine and Pyrimidine synthesis. This scenario is mentioned there.
 

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A 3 year old Caucasian boy is brought by his parents to the clinic because they think he looks "pale" and "weak". On examination the boy is lethargic and has pale conjunctivae. Blood analysis denotes megaloblastic anemia. Urine analysis shows excess carbamoyl phosphate derivative in the urine. There are no other abnormalities. The most likely cause for this boy's condition is:

A. Vitamin B12 deficiency
B. Folic acid excess
C. Ornithine transcarbamoylase deficiency
D. Orotidine 5'-phosphate decarboxylase deficiency
E. Carbamoyl phosphate synthetase I deficiency

Please attach an explanation to your answer.
Urine analysis shows excess carbamoyl derivative in urine, is it orotic acid you are referring to?
oroticaciduria along with megaloblastic anemia can give a clue to the right answer( i.e. D)thats the only way I can understand this Q or is there any other explanation?
 
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