Which out of the following conditions is associated with hypouricemia?
A. Lesch Nyhan syndrome
B. Adenosine deaminase deficiency
C. Over activity of PRPP synthetase
D. Over activity of Amido transferase
E. Von Gierke’s disease
Answer- The correct answer is Adenosine deaminase deficiency.
Adenosine deaminase deficiency, also called ADA deficiency or ADA-SCID is an Autosomal recessive disorder that causes immunodeficiency. It accounts for about 15% of all cases of severe combined immunodeficiency (SCID). The SCID syndrome is characterized by gross functional impairment of both humoral and cell-mediated immunity and by susceptibility to devastating fungal, bacterial, and viral infections.
Adenosine deaminase- catalyzes the conversion of adenosine to Inosine and deoxy adenosine to deoxy Inosine (figure).Defects in this enzyme results in the accumulation of adenosine and deoxyadenosine, as well as Inosine. Excessive deoxy adenosine that accumulates is either excreted or is converted to dATP. High concentrations of dATP are found in the lymphocytes of patients with adenosine deaminase deficiency. The enzyme Ribonucleotide Reductase is inhibited by the abnormally high concentration of dATP. As a result the concentration of other deoxy ribonucleotides is also reduced, and this, inhibits DNA synthesis. The actively proliferating cells like T and B lymphocytes are most affected by impaired DNA synthesis. Intracellular accumulation of adenosine and deoxyadenosine nucleotides triggers the apoptosis of immature T and B lineage cells. Thus the proliferation, differentiation and the maturation of T and B lymphocytes are most affected, as a result the immune response is grossly decreased and the affected person becomes highly susceptible to infections.
Figure- Adenosine deaminase catalyzes conversion of adenosine to inosine its under activity leads to impaired uric acid formation
As regards other options,
- Lesch Nyhan syndrome occurs due to deficiency of HGPRT (Hypoxanthine Guanine Phospho Ribosyl Transferase) enzyme, its deficiency is associated with hyperuricemia due to degradation of unsalvaged purines as well as due to the reason that unutilized PRPP which would otherwise have been utilized in Salvage pathway is channeled to denovo pathway, excess purine nucleotide biosynthesis leads to excess degradation with the resultant hyperuricemia.
- PRPP synthetase catalyzes the conversion of Ribose-5-P to PRPP (phosphoribosyl pyro phosphate); it’s over activity leads to hyperactive de novo pathway of purine nucleotide biosynthesis, more synthesis, more degradation and resultant hyperuricemia.
- Amido transferase is another enzyme of de novo pathway of purine nucleotide biosynthesis. It catalyzes the conversion of PRPP to 5’phosphoribosylamine. It’s over activity is also associated with hyperuricemia due to the similar reason as that of PRPP synthetase.
- Von Gierke’s disease is associated with impaired activity of Glucose-6-phosphatase. Excess Glucose-6-P is channeled to HMP pathway with the resultant excess formation of PRPP and overactive de novo pathway and resultant hyperuricemia.