Purine nucleoside phosphorylase deficiency: a mutation update.

Area of Science:

• Biochemistry
• Genetics
• Immunology

Background:

• Purine nucleoside phosphorylase (PNPase) deficiency is an autosomal recessive disorder impacting purine metabolism.
• Clinical manifestations include severe immunodeficiency, neurological dysfunction, and autoimmunity.
• Hypouricemia is a biochemical indicator, but not always present.

Purpose of the Study:

• To report biochemical and genetic findings in a cohort of seven PNPase-deficient patients.
• To identify novel mutations associated with PNPase deficiency.
• To assess the utility of hypouricemia as a diagnostic marker.

Main Methods:

• Biochemical analysis of purine metabolites in urine.
• Mutation analysis of the PNPase gene.
• Literature review of previously reported cases.

Main Results:

• Elevated levels of inosine, deoxyinosine, guanosine, and deoxyguanosine in urine for all patients.
• Identification of seven distinct mutations, including three novel ones (c.770A>G, c.257A>G, c.199C>T).
• Five out of seven patients had normal plasma uric acid levels.

Conclusions:

• PNPase deficiency diagnosis should be considered even in the absence of hypouricemia.
• Novel mutations expand the spectrum of known genetic variants causing PNPase deficiency.
• Genetic and biochemical analyses are crucial for accurate diagnosis and understanding disease mechanisms.