Adenine phosphoribosyltransferase deficiency

At least 40 mutations in the APRT gene have been found to cause adenine phosphoribosyltransferase (APRT) deficiency, a condition that affects the kidneys and urinary tract. Most of these mutations change single protein building blocks (amino acids) in the APRT enzyme. The mutations that cause APRT deficiency are categorized into two groups known as the APRT*J allele and the APRT*Q0 allele. The APRT*J allele consists of one mutation that replaces the amino acid methionine with the amino acid threonine at position 136 in the APRT enzyme (written as Met136Thr or M136T). This mutation reduces the function of the enzyme. The M136T mutation occurs almost exclusively in Japanese individuals with the condition; most affected individuals have this mutation on both copies of the APRT gene in each cell. The APRT*Q0 allele consists of all other APRT gene mutations. The most common of these mutations (written IVS4+2insT) alters the genetic instructions used to make the enzyme, resulting in an abnormally short, nonfunctional enzyme. This mutation is estimated to occur in 40 percent of affected Europeans.

APRT gene mutations lead to a lack of functional enzyme that prevents the conversion of adenine to AMP. As a result, adenine is converted to another molecule called 2,8-dihydroxyadenine (2,8-DHA). 2,8-DHA crystallizes in urine, forming stones in the kidneys and urinary tract. As a result, kidney function can decline, which may lead to end-stage renal disease (ESRD), a life-threatening failure of kidney function.