Disorders of Purine and Pyrimidine metabolism

Adenosine Deaminase (ADA) deficiency

• ADA irreversibly deaminates adenosine converting it to inosine
• Cells ^^cannot make DNA and can’t divide^^
• In its sever form it ^^affects T and B lymphocytes^^ ($severe combined immunodeficiency disease (SCID$))
    * a defect in both cellular and humoral immunity
• can cause death from massive infection before patient reaches the age of 2 years

Symptoms of ADA deficiency

Symptoms develop before 6 months of age

Earliest symptoms include:

• pneumonia
• chronic diarrhea
• widespread skin rashes
• development delay

Purine nucleoside phosphorylase (PNP) deficiency

Associated with an immunodeficiency involving ^^T-cell function^^ only, sparing B-cells.

Can cause:

• $Hypouricemia$: serum uric acid concentration of less than 2.0 mg/dL
• $Hypouricosuria$: presence of an unusually low amount of uric acid in the urine.

Immune dysfunction appear to result from @@accumulation of dGTP and dATP@@, which allosterically inhibit ribonucleotide reductase, depleting cells from DNA precursors, especially dCTP.

Hypouricemia

• rare condition due to severe ==deficiency of xanthine oxidase enzyme==
• associated with accumulation of hypoxanthine and xanthine resulting in $<strong>xanthinuria</strong>$

Disorder of Pyrimidine Metabolism

$<strong>Hereditary orotic aciduria:</strong>$

results from a defect in de novo synthesis of pyrimidine nucleotides

defect in one or both of the activities of:

• ^^orotate phosphoribosyltransferase^^
• ^^orotidine decarboxylase^^

Characterized by:

• severe anemia
• growth retardation
• high levels of orotic acid excretion