APRT deficiency

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...

Hypoxanthine-guanine phosphoribosyl-transferase (HPRT) deficiency is the cause of Lesch-Nyhan disease. Adenine phosphoribosyl-transferase (APRT) deficiency causes renal calculi. The activity of each enzyme is readily determined on spots of whole blood on filter paper. This unit describes a method for detecting deficiencies of HPRT and APRT.

Adenine phosphoribosyltransferase (APRT) deficiency, a rare inborn error inherited as an autosomic recessive trait, presents with 2,8-dihydroxyadenine (2,8-DHA) crystal nephropathy. We describe clinical, biochemical and molecular findings in a renal transplant recipient with renal failure, 2,8-DHA stones and no measurable erythrocyte APRT activity. Homozygous C > G substitution at -3 in the splicing site of exon 2 (IVS2 -3 c > g) was found in the APRT gene. The patient's asymptomatic brother was heterozygous for such mutation, and his APRT activity was 23% of controls...

We describe two patients that had a history of recurrent renal stones and chronic renal insufficiency. The first case was a 51-year-old man with an adenine phophoribosyltransferase (APRT) deficiency who was diagnosed only after he had been referred for severe renal failure requiring hemodialysis. This led to a screening of the entire family, which identified six carriers and an additional affected relative (a 41-year-old man and the second case reported herein). Genetic analysis of the APRT gene revealed an atypical mutation previously described only once in a compound heterozygote...

An 18-year-old man was admitted to our hospital because of convulsive seizure. He had psychomotor retardation and intellectual disability from childhood, and had been diagnosed with attention deficit-hyperactivity disorder when he was 12 years old. He showed mental deficit (Wechsler Adult Intelligence Scale-Revised: IQ 52) and tendon hyperreflexia without pathological reflexes, but no involuntary movements or self-injurious behavior. As he had hyperuricemia, we measured the activity of hypoxanthine-guanine phosphoribosyltransferase (HPRT) and adenine phosphoribosyltransferase (APRT) in erythrocytes...

Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive enzyme defect of purine metabolism that usually manifests as 2,8-dihydroxyadenine (2,8-DHA) nephrolithiasis and more rarely chronic kidney disease. The disease is most often misdiagnosed and can recur in the renal allograft. We analyzed nine patients with recurrent 2,8-DHA crystalline nephropathy, in all of whom the diagnosis had been missed prior to renal transplantation. The diagnosis was established at a median of 5 (range 1...

BACKGROUND: Adenine phosphoribosyltransferase deficiency (APRTD) is an under estimated genetic form of kidney stones and/or kidney failure, characterized by intratubular precipitation of 2,8-dihydroxyadenine crystals (2,8-DHA). Currently, five pathologic allelic variants have been identified as responsible of the complete inactivation of APRT protein. CASE PRESENTATION: In this study, we report a novel nonsense mutation of the APRT gene from a 47- year old Italian patient...

Inborn errors of purine metabolism exhibit broad neurological, immunological, haematological and renal manifestations. Limited awareness of the phenotypic spectrum, the recent descriptions of newer disorders and considerable genetic heterogeneity, have contributed to long diagnostic odysseys for affected individuals. These enzymes are widely but not ubiquitously distributed in human tissues and are crucial for synthesis of essential nucleotides, such as ATP, which form the basis of DNA and RNA, oxidative phosphorylation, signal transduction and a range of molecular synthetic processes...

Adenine phosphoribosyltransferase (APRT) deficiency is a rare inherited metabolic disorder that leads to the formation and hyperexcretion of 2,8-dihydroxyadenine (DHA) into urine. The low solubility of DHA results in precipitation and formation of urinary crystals and kidney stones. The disease can be present as recurrent urolithiasis or nephropathy secondary to crystal precipitation into renal parenchyma (DHA nephropathy). The diagnostic tools available, including stone analysis, crystalluria, and APRT activity in red blood cells, make the diagnosis easy to confirm when APRT deficiency is suspected...

6-Fluoro-3-hydroxy-2-pyrazinecarboxamide (T-705) is a novel antiviral compound with broad activity against influenza virus and diverse RNA viruses. Its active metabolite, T-705-ribose-5'-triphosphate (T-705-RTP), is recognized by influenza virus RNA polymerase as a substrate competing with GTP, giving inhibition of viral RNA synthesis and lethal virus mutagenesis. Which enzymes perform the activation of T-705 is unknown. We here demonstrate that human hypoxanthine guanine phosphoribosyltransferase (HGPRT) converts T-705 into its ribose-5'-monophosphate (RMP) prior to formation of T-705-RTP...

We describe an infant affected by adenine phosphoribosyltransferase (APRT) deficiency diagnosed at 18 months of age with a de novo mutation that has not been previously reported. APRT deficiency is a rare defect of uric acid catabolism that leads to the accumulation of 2,8 dihydroxyadenine (2,8-DHA), a highly insoluble substance excreted by the kidneys that may precipitate in urine and form stones. The child suffered from renal colic due to a stone found in the peno-scrotal junction of the bulbar urethra. Stone spectrophotometric analysis allowed us to diagnose the disease and start kidney-saving therapy in order to avoid irreversible chronic kidney damage...

Adenine phosphoribosyltransferase (APRT) deficiency, cystinuria, Dent disease, familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), and primary hyperoxaluria (PH) are rare but important causes of severe kidney stone disease and/or chronic kidney disease in children. Recurrent kidney stone disease and nephrocalcinosis, particularly in pre-pubertal children, should alert the physician to the possibility of an inborn error of metabolism as the underlying cause. Unfortunately, the lack of recognition and knowledge of the five disorders has frequently resulted in an unacceptable delay in diagnosis and treatment, sometimes with grave consequences...

Adenine phosphoribosyltransferase (APRT) deficiency is an enzyme deficiency associated with purine metabolism, a hereditary disease that causes recurrent 2, 8-DHA stone formation due to a complete or partial APRT defect and slowly damages the renal function. Since APRT deficiency can be treated to prevent its progression to renal insufficiency, it is important to detect APRT gene mutations and make a definite diagnosis early. A 3.5-year-old girl presented with painful urination and dysuria, and was admitted to our hospital...

The study of gene function has been greatly facilitated by the development of strategies to modify genomic DNA. Gene targeting is one of the most successfully applied techniques used to examine the roles of specific genes in a wide variety of model systems from yeast to mammals. Our laboratory has pioneered the use of the Chinese hamster ovary (CHO) cell culture model system to study pathways of DNA repair and recombination at the hemizygous CHO APRT locus. By using a simple and effective gene targeting method, we have generated a number of DNA repair-deficient cell lines that have been used in targeted recombination experiments to investigate pathways of recombinational repair in somatic mammalian cells...

Several alkylanilines with structures more complex than toluidines have been associated epidemiologically with human cancer. Their mechanism of action remains largely undetermined, and there is no reported evidence that it replicates that of multicyclic aromatic amines even though the principal metabolic pathways of P450-mediated hydroxylation and phase II conjugation are very similar. As a means to elucidate their mechanisms of action, lethality and mutagenicity in the adenine phosphoribosyltransferase (aprt (+/-)) gene induced in several Chinese hamster ovary cell types by 2,6- and 3,5-dimethylaniline (2,6-DMA, 3,5-DMA) and their N- and ring-hydroxyl derivatives (N-OH-2,6-DMA, N-OH-3,5-DMA, 2,6-DMAP, 3,5-DMAP) were assessed...

Complete adenine phosphoribosyltransferase (APRT) deficiency is a rare inherited metabolic disorder that leads to the formation and hyperexcretion of 2,8-dihydroxyadenine (DHA) into urine. The low solubility of DHA results in precipitation of this compound and the formation of urinary crystals and stones. The disease can present as recurrent urolithiasis or nephropathy secondary to crystal precipitation into renal parenchyma (DHA nephropathy). The diagnostic tools available-including stone analysis, crystalluria, and APRT activity measurement-make the diagnosis easy to confirm when APRT deficiency is suspected...

The loss of the H(2)O(2) scavenger protein encoded by Prdx1 in mice leads to an elevation of reactive oxygen species (ROS) and tumorigenesis of different tissues. Loss of heterozygosity (LOH) mutations could initiate tumorigenesis through loss of tumor suppressor gene function in heterozygous somatic cells. A connection between the severity of ROS and the frequency of LOH mutations in vivo has not been established. Therefore, in this study, we characterized in vivo LOH in ear fibroblasts and splenic T cells of 3-4 month old Prdx1 deficient mice...

Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder characterized by 2,8-dihydroxyadenine (2,8-DHA) crystalluria that can cause nephrolithiasis and chronic kidney disease. The aim of our study was to assess the clinical presentation, diagnosis, and outcome of APRT deficiency in a large pediatric cohort. All pediatric cases of APRT deficiency confirmed at the same French reference laboratories between 1978 and 2010 were retrospectively reviewed. Twenty-one patients from 18 families were identified...

We report a case of bilateral renal calculi in a 1-year-old female with adenine phosphoribosyl transferase (APRT) partial deficiency. She initially visited another institution with high fever as the major complaint. Computed tomography revealed a bilateral renal stone and left hydro nephrosis. In the urine, there were 2, 8-dihydroxyadenine (DHA) crystals. An analysis of the APRT gene revealed the APRT deficiency and the genotype to be APRT*J/APRT*Q0. We performed extracorporeal shock wave lithotripsy (ESWL) under general anesthesia, and as dissolution therapy we administered Meylon through the nephrostomy and citric acid orally...

OBJECTIVE: To explore the effects of heroin on purine nucleotides metabolism in rat brain. METHODS: Biochemical changes in association with heroin administration were compared between heroin-administered rats and non-heroin rats. HPLC method was used to detect the absolute content of purine nucleotides in brain tissues. Concentrations of uric acid (UA), blood urea nitrogen (BUN) and creatinine (Cre) in plasma were measured. Enzymatic activities of adenosine deaminase (ADA) and xanthine oxidase (XO) in brain tissue were analyzed...