Purine nucleoside phosphorylase deficiency (PNP deficiency)
Incidence
It is an autosomal recessive disorders with decreased T cells and lymphopenia and antibody deficiency. This disorder has been described in at least 30 patients.
Clinical Characteristics
The age of presentation has varied, but it has generally occurred in the first 4 years of life, associated with neurological or immunological problems, or both. The main clinical presentation is recurrent infections. Symptoms usually occur towards the end of the patient's second year and persist during the 5th or 6th first years. Children are particularly prone to viral infections (chicken pox, mumps, cytomegalovirus) and vaccines, but suppurant bacterial infections have also been noted. One third of all patients have anemia, 2/3 have neurological signs (ataxia, spastic tetraplegy and tremor). Severe immune deficiency is usually found, affecting cell immunity and causing markedly low levels of T-cells. Purine nucleoside phosphorylase deficiency is an autosomal recessive inherited disorder that interrupts both the catabolism of inosine into hypoxanthine and guanosine into guanine, and leads to the accumulation of guanosine, inosine, and their deoxified byproducts. As a result levels of guanine, hypoxanthine, xanthine and uric acid are depressed. Diagnosis is suggested by T-cell deficiency combined with severe hypouricemia, and confirmed by measuring enzymatic deficiency in red blood cells. The disease is spontaneously severe. Patients are treated symptomatically and preventively for infections, but bone marrow transplantation and repeated irradiated blood transfusions are the only real treatments. Antenatal diagnosis is feasible.
Precipitants
No.
Provocation Tests
No.
Diagnostic Procedures
EB-R. Reduced erythrocyte purine nucleoside phosphorylase activity. Diagnosis is suggested by T-cell deficiency combined with severe hypouricemia, and confirmed by measuring enzymatic deficiency in red blood cells. The finding of undetectable, or extremely low, blood and urine uric acid levels in a child with neurological defects, or recurrent viral infection, is suggestive of PNP deficiency. The biochemical abnormality may be established by the presence of grossly raised amounts of inosine, guanosine, deoxyinosine and deoxyguanosine in plasma (50, 10, 5 and 5 µmol/l respectively) compared with normally undetectable levels. In urine the same compounds are excreted in excess in the same relative proportions, total purine excretion (in the form of nucleosides) being increased two- to fourfold on a creatinine basis. In severe cases no uric acid is detectable in any body fluid, but significant levels have been found in late presenters.