Adenine phosphoribosyltransferase deficiency (APRT):
This is a rare autosomal recessive disorder that cause by deficiency of APRT enzyme. APRT catalyse the reaction between adenine and phosphoribosyl pyrophosphate and forms AMP. Deficiency of APRT leads adenine accumulation which is oxidized to 2,8-dihyroxyadenine and precipitates in the urinary tract. Diagnosis is by detecting elevated levels of 2,8-dihyroxyadenine, 8-hyroxyadenine, and adenine in urine.
Disorders of purine nucleotide synthesis
Phosphoribosylpyrophosphate synthetase superactivity:
This X-linked recessive disorder causes purine overproduction. Excess purine after degradation, resulting in hyperuricemia, gout, neurologic and developmental abnormalities.
Disorder of purine catabolism
Adenosine deaminase deficiency :
ADA converts adenosine and deoxyadenosine to inosine and deoxyinosine, which are further broken down and excreted out from the body. Enzyme deficiency results in accumulation of adenosine which is further converted to its ribonucleotide and deoxyribonucleotide (dATP) forms by cellular kinase activity. The increase in dATP results inhibition of ribonucleotide reductase and underproduction of other deoxyribonucleotides. As a result, DNA replication is compromised. Immune cells are especially sensitive to this defect because ADA is most active in lymphocytes. Thus adenosin e deaminase deficiency causes one form of severe combined immunodeficiency (SCID).
Disorders of pyrimidine metabolism
Uridine monophosphate synthase deficiency:
Uridine monophosphate is the enzyme that catalyzes formation of UMP. Its gene is present on 3q13 location. This bifunctional enzyme has 2 subunits-orotate phosphoribosyltransferase and orotidine-5 ' -monophosphate decarboxylase. These enzymes work in the last 2 steps of UMP synthesis. With its deficiency due to mutation, orotic acid accumulates in body, causing megaloblastic anemia, orotic crystalluria and nephropathy, cardiac malformations, strabismus, and recurrent infections.
