APRT deficiency

BACKGROUND: Adenine phosphoribosyltransferase (APRT) deficiency is a rare, hereditary cause of kidney stones and chronic kidney disease (CKD), characterized by 2,8-dihydroxyadenine (DHA) renal parenchymal crystal deposition. The aim of this study was to examine outcomes of kidney transplantation in APRT deficiency patients. METHODS: Included were 13 patients in the APRT Deficiency Registry of the Rare Kidney Stone Consortium, 2 from Westmead Hospital in Sydney, Australia, and 2 from Necker Hospital in Paris, France...

BACKGROUND: Adenine phosphoribosyl transferase (APRT) deficiency is a rare genetic form of kidney stones and/or kidney failure characterized by intratubular precipitation of 2,8 dihydroxyadenine crystals. Early diagnosis and prompt management can completely reverse the kidney injury. CASE PRESENTATION: 44 year old Indian male, renal transplant recipient got admitted with acute graft dysfunction. Graft biopsy showed light brown refractile intratubular crystals with surrounding giant cell reaction, consistent with APRT deficiency...

BACKGROUND: Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder of adenine metabolism that results in excessive urinary excretion of the poorly soluble 2,8-dihydroxyadenine (DHA), leading to kidney stones and chronic kidney disease. The purpose of this study was to assess urinary DHA excretion in patients with APRT deficiency, heterozygotes and healthy controls, using a recently developed ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) assay...

Deciding whether to accept a donor with nephrolithiasis is a multifaceted task because of the challenge of finding enough suitable donors while at the same time ensuring the safety of both donors and recipients. Until not long ago, donors with a history of renal stones or with stones emerging during screening on imaging were not considered ideal, but recent guidelines have adopted less stringent criteria for potential donors at risk of stones. This review goes through the problems that need to be approached to arrive at a wise clinical decision, balancing the safety of donors and recipients with the need to expand the organ pool...

BACKGROUND: Adenine phosphoribosyltransferase (APRT) deficiency is a hereditary purine metabolism disorder that causes kidney stones and chronic kidney disease (CKD). The purpose of this study was to examine the course of APRT deficiency in patients who presented in childhood. METHODS: The disease course of 21 (35%) patients in the APRT Deficiency Registry of the Rare Kidney Stone Consortium, who presented with manifestations of APRT deficiency and/or were diagnosed with the disorder before the age of 18 years, was studied...

The incidence of urolithiasis in children has shown an increase in recent years which may be attributed to changing dietary patterns, sedentary lifestyles, and obesity. Among the various etiologies for renal stones in children, two rare entities worth mentioning are cystinuria and 2, 8-dihydroxyadenine (DHA) urolithiasis. Cystinuria is an inherited cause of nephrolithiasis which occurs due to impaired cystine reabsorption in the renal proximal tubule. 2, 8-DHA urolithiasis is an inherited autosomal recessive disease resulting in urinary stone disease secondary to deficiency of adenine phosphoribosyltransferase (APRT) activity...

Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder which leads to accumulation of poorly soluble 2,8-dihydroxyadenine in kidneys resulting in nephrolithiasis as well as chronic kidney disease from crystal nephropathy. This report describes a 55-year-old previously fit man who presented with shortness of breath and the investigative pathway that eventually led to a diagnosis of APRT deficiency. Early diagnosis has aided in timely institution of allopurinol, thereby improving his renal function and possibility of weaning off renal replacement therapy...

Adenine phosphoribosyltransferase (APRT) deficiency (OMIM #614723) is a rare autosomal recessive defect in the purine salvage pathway that causes excessive production of 2,8-dihydroxyadenine, leading to nephrolithiasis and chronic kidney disease (CKD). This case report describes the natural history of CKD in untreated APRT deficiency. We describe a novel APRT mutation (chr16:88877985 G / C; c.195 C>/G; p.His54Asp) presenting with CKD without nephrolithiasis. The patient initially required dialysis, but kidney function improved with allopurinol...

INTRODUCTION: Adenine phosphoribosyltransferase (APRT) deficiency is a rare, but significant, cause of kidney stones and progressive chronic kidney disease. The optimal treatment has not been established. The purpose of this pilot study was to compare the effect of the xanthine oxidoreductase inhibitors allopurinol and febuxostat on urinary 2,8-dihydroxyadenine (DHA) excretion in APRT deficiency patients. MATERIALS AND METHODS: Patients listed in the APRT Deficiency Registry of the Rare Kidney Stone Consortium, currently receiving allopurinol therapy, were invited to participate...

Complete deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity causes Lesch Nyhan disease (LND), characterized by hyperuricemia, severe action dystonia, choreoathetosis, ballismus, cognitive and attention deficit and self-injurious behavior. Partial HPRT deficiency is present in patients with Lesch-Nyhan variant (LNV), who present with HPRT-related gout and a variable degree of neurological involvement. The diagnosis of HPRT deficiency relies on clinical, biochemical, enzymatic and molecular data...

Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive error of purine metabolism resulting in the generation of 2,8-dihydroxyadenine (DHA), a highly insoluble metabolite of adenine, which can cause radiolucent urolithiasis. This is the second case of DHA stone being reported in India and the first case in India to document the mutation of the APRT gene on blood DNA analysis.

Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder that results in irreversible renal damage due to 2,8-dihydroxyadenine (DHA) nephropathy. A 28-year-old man underwent living-related kidney transplantation for chronic kidney disease of unknown etiology. Numerous spherical brownish crystals observed in his urinary sediment on postoperative day 3 and were observed within the tubular lumen of renal allograft biopsy specimens on postoperative day 7. After a genetic diagnosis, febuxostat treatment was started on postoperative day 7, with the dosage gradually increased to 80 mg/day until complete the disappearance of 2,8-DHA crystals...

Background: Recurrent urolithiasis is troublesome for both patient and clinician, and in most cases, an underlying cause is not found. An important and underdiagnosed cause is adenine phosphoribosyltransferase (APRT) deficiency that gives rise to 2,8-dihydroxyadenine (2,8-DHA) stones. If diagnosed early, patient morbidity as well as the financial cost of treating stone recurrence can be avoided with simple medical therapy. Case Presentation: A 36-year-old white, Caucasian male with recurrent urolithiasis was found to have 2,8-DHA stones...

Di-(2-ethylhexyl) phthalate (DEHP), the common plasticizer used in the production of polyvinyl chloride, can be converted to the more potent metabolite mono-ethylhexyl phthalate (MEHP). Epidemiological studies have shown an association with elevated induction of rat hepatic cancer and reproductive toxicity in response to MEHP exposure. However, the mechanism of genotoxicity and carcinogenicity induced by MEHP treatment remains unclear. As a means to elucidate the mechanisms of action, lethality and mutagenicity in the adenine phosphoribosyltransferase (aprt+/-) gene induced in several CHO cell types by MEHP were assessed...

Homologous recombination (HR) is a DNA double-strand break (DSB) repair pathway that protects the genome from chromosomal instability. RAD51 mediator proteins (i.e. paralogs) are critical for efficient HR in mammalian cells. However, how HR-deficient cells process DSBs is not clear. Here, we utilized a loss-of-function HR-reporter substrate to simultaneously monitor HR-mediated gene conversion and non-conservative mutation events. The assay is designed around a heteroallelic duplication of the Aprt gene at its endogenous locus in isogenic Chinese hamster ovary cell lines...

Adenine phosphoribosyltransferase (APRT) deficiency is a hereditary disorder that leads to excessive urinary excretion of 2,8-dihydroxyadenine (DHA), causing nephrolithiasis and chronic kidney disease. Treatment with allopurinol or febuxostat reduces DHA production and attenuates the renal manifestations. Assessment of DHA crystalluria by urine microscopy is used for therapeutic monitoring, but lacks sensitivity. We report a high-throughput assay based on ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) for quantification of urinary DHA...

BACKGROUND: Adenine phosphoribosyltransferase (APRT) deficiency is a purine metabolism disorder causing kidney stones and chronic kidney disease (CKD). The course of nephrolithiasis and CKD has not been well characterized. The objective of this study was to examine long-term kidney outcomes in patients with APRT deficiency. STUDY DESIGN: An observational cohort study. SETTING & PARTICIPANTS: All patients enrolled in the APRT Deficiency Registry of the Rare Kidney Stone Consortium...

BACKGROUND: Adenine phosphoribosyltransferase (APRT) deficiency is an uncommon genetic cause of chronic kidney disease due to crystalline nephropathy. METHODS: A case of a Chinese boy with APRT deficiency presenting with severe acute kidney injury secondary to obstructive uropathy from multiple renal calculi was reviewed. RESULTS: The patient underwent staged removal of the calculi. Infrared spectrometry of the renal calculi showed 2,8-dihydroxyadenine...

The purine salvage pathway plays a major role in the nucleotide production, relying on the supply of nucleobases and nucleosides from extracellular sources. Although specific transporters have been suggested to be involved in facilitating their transport across the plasma membrane in mammals, those which are specifically responsible for utilization of extracellular nucleobases remain unknown. Here we present the molecular and functional characterization of SLC43A3, an orphan transporter belonging to an amino acid transporter family, as a purine-selective nucleobase transporter...

Here we report a case of a 2,8-dihydroxyadenine (2,8-DHA) stone. A 48-year-old woman arrived at our hospital with left flank pain. She was diagnosed with a left ureteral stone. Extracorporeal shock wave lithotripsy (ESWL) was tried, but the left ureteral stone was radiolucent and ESWL was not effective. Transurethral ureterolithotripsy (TUL) was successful. An analysis of the stone revealed 2,8-DHA. A 2,8-DHA stone is caused by adenine phosphoribosyltransferase (APRT) deficiency. By genetic tests, she was diagnosed with APRT deficiency...