The following points highlight the six major diseases caused due to errors in nucleic acid metabolism. The diseases are: 1. Lesch-Nyhan Syndrome 2. Hereditary Xanthinuria 3. Orotic Aciduria 4. Hypouricemia 5. Von Gierke’s Disease 6. Reye’s Syndrome.
Errors in Nucleic Acid Metabolism: Disease # 1. Lesch-Nyhan Syndrome:
a. This condition is characterized by the complete deficiency of phosphoribosyl transferase, which causes hypoxanthine or guanine to form a nucleotide with PRPP (5′- phosphoribosyl – 1′- pyrophosphate). These purines are thus available for the formation of uric acid.
b. This disorder is X-linked in its inheritance.
c. This appears in childhood as a severe neurological syndrome, which is sometimes accompanied by gout. The urinary uric acid amount is five to six times the normal.
d. Hypothyroidism, hypo- and hyperparathyroidism are accompanied by hyperuricemia.
e. Hypertension is accompanied by increased plasma uric acid. Such patients show an increased tendency to myocardial infarction, which is also a cause of hyperuricemia.
f. It can be prevented or diminished by the administration of allopurinol, an analogue of hypoxanthine. Allopurinol inhibits xanthine oxidase due to which uric acid cannot be formed.
Errors in Nucleic Acid Metabolism: Disease # 2. Hereditary Xanthinuria:
a. In this rare genetic disorder, there is the deficiency of xanthine oxidase which leads to the diminished level of blood uric acid (1 mg/100 ml or less).
b. The urinary excretion contains large amounts of xanthine with lesser amounts of hypoxanthine.
c. Urinary calculi composed of xanthine may be produced.
Errors in Nucleic Acid Metabolism: Disease # 3. Orotic Aciduria:
a. This is an inherited disorder which causes the excessive production of orotic acid. This occurs by the deficiency of orotatc phosphoribosyl transferase.
b. The urinary excretion consists of large amounts of pyrimidine nucleotide precursor.
c. The urine becomes cloudy on cooling with the deposition of needle-shaped crystals of orotic acid.
d. Children affected by this condition develop a severe megaloblastic anemia with physical and mental retardation.
e. Administration of uridine improves this condition significantly.
Errors in Nucleic Acid Metabolism: Disease # 4. Hypouricemia:
a. This is due to a genetic defect or to severe liver damage.
b. The deficiency of the enzyme xanthine oxidase causes hypouricemia and increased excretion of hypoxanthine and xanthine.
c. Patients may exhibit Xanthinuria and Xanthine lithiasis in severe xanthine oxidase deficiency.
Errors in Nucleic Acid Metabolism: Disease # 5. Von Gierke’s Disease:
a. This disease is associated with the purine over-production and hyperuricemia.
b. There is also enhanced generation of the PRPP.
c. The associated lactic acidosis elevates the renal threshold for urate, increasing total body urates. (The rest is already mentioned in Glycogen storage disease. Add this to it).
Errors in Nucleic Acid Metabolism: Disease # 6. Reye’s Syndrome:
a. The orotic aciduria accompanies this syndrome.
b. This syndrome exhibits inability of severely damaged mitochondria to use carbamoyl phosphate which is available for cystosotic over- production of orotic acid.