Purine and pyrimidine synthesis and metabolism disorders: Pathology review

Three kids are brought to the clinic by three very concerned mothers.

The first one’s Carl, a 10 month old boy that, according to his mother, is always sick with bronchitis and diarrhea.

On physical examination, you notice that Carl is quite small for his age.

Laboratory studies are obtained, showing an absolute lymphocyte count of 2,000 cells per cubic millimeter.

A sputum culture reveals that Carl’s bronchitis is caused by a fungal infection by Pneumocystis jirovecii.

Next comes Mark, a 2 year old boy with aggressive and self-destructive behavior, such as constantly biting his lips, tongue, and fingers.

In addition, Mark doesn’t seem to be able to walk or speak a word.

His mother tells you that her younger brother, so Mark’s uncle, was diagnosed with a rare disease that caused mental retardation, and she’s worried Mark may have it too.

Upon physical exam, you notice some orange sand-like deposits in his diapers.

Laboratory studies show elevated levels of uric acid in his blood.

Finally, you see Laura, a 4 month old girl with a history of anemia that was diagnosed some days after birth.

Since then, Laura has been on a bottle-feeding regimen with folate and vitamin B12 supplementation; however, her anemia is not getting any better.

On examination, you notice cloudy urine that left some residues on Laura’s diaper, so you ask for a urinalysis.

Results revealed that the residues are orotic acid crystals.

Based on the initial presentation, all three cases seemed to be due to purine and pyrimidine metabolism disorder.

But first, a bit of biochemistry review.

Normally, each nucleotide can be broken down into a sugar that’s either a deoxyribose in DNA or a ribose in RNA, followed by one to three phosphate groups, and a nucleobase, which can be either a purine or a pyrimidine.

There are two purine bases, adenine and guanine; and three pyrimidine bases, cytosine, thymine, and uracil.

Now, the nucleoside based on adenine and ribose is adenosine, and a nucleotide based on adenosine and one phosphate would be adenosine monophosphate, or AMP for short; whereas the same combination with a deoxyribose would be deoxyadenosine monophosphate, or dAMP; and the same naming convention applies to all the other nucleobases.

Now, there are two ways our cells can make nucleotides, one is de novo synthesis, meaning that they are made from scratch, and the other is via the salvage pathway, by recycling nucleotides.