Adenine phosphoribosyl transferase (APRT) deficiency and a novel sequence variant in APRT with phenotypic diversity and a literature review

Abstract

Adenine phosphoribosyl transferase (APRT) deficiency is an autosomal recessive disorder and a rare cause of urolithiasis due to mutations in APRT (OMIM #102600). APRT deficiency results in increased urinary excretion of 2,8‐dihydroxyadenine (DHA) which can cause urolithiasis and kidney failure. However, with prompt diagnosis, patients with APRT deficiency can be treated with xanthine oxidoreductase inhibitors which decrease urinary DHA excretion and improve outcomes. We report a pair of siblings, an 11‐year‐old brother and his 14‐year‐old sister with compound heterozygous variants c.270del (p.Lys91Serfs*46) and c.484_486del (p.Leu162del) in APRT with variable clinical presentation of APRT deficiency. The brother presented at 17 months of age with urolithiasis and severe acute kidney injury. His elder sister remained well and asymptomatic with normal kidney function and did not develop renal calculi. Brownish disk or sphere‐like crystals with both concentric and radial markings were reported on urine microscopy in the sister on screening. The sister's diagnosis was confirmed with further laboratory evidence of absent red cell lysate APRT activity with corresponding elevated levels of urinary DHA. In conclusion, we identified a novel mutation in the APRT gene in a pair of siblings with greater phenotypic severity in the male.

Chemo-Enzymatic Generation of Highly Fluorescent Nucleoside Analogs Using Purine-Nucleoside Phosphorylase

“…It would be interesting to examine analogous possibilities of other enzymatic systems, for example, phosphoribosyl transferases, catalyzing the formation of nucleotides from nucleobases and 5-phosphoribose-1-pyrophosphate (PrPP), a group of enzymes which are extensively investigated because of their medical significance [ 103 , 104 , 105 ]. Various bacterial enzymatic systems, like deoxy-ribosyl transferases, phosphoribosyl transferases, and/or nucleoside hydrolases (acting in non-aqueous media) may also be useful, but their specificities towards fluorescent or fluorogenic analogs are mostly unknown.…”