succinyladenosine and Purine-Pyrimidine-Metabolism--Inborn-Errors

Stable isotope dilution coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) is the sensitive method for screening for various inherited metabolic disorders using dried blood spots (DBSs). We present a method for LC-MS/MS determination of succinyladenosine (SAdo) and succinylaminoimidazole carboxamide riboside (SAICAr), biomarkers for adenylosuccinate lyase deficiency (dADSL), in DBS.. SAICAr and SAdo were separated on a Symmetry-C18 column and detected using positive electrospray ionisation in selected reaction monitoring mode. The quantification was performed using the isotopically labelled internal standards SAdo-(13)C4 and SAICAr-(13)C4, which were prepared via ADSL-catalysed reactions of fumarate-(13)C4 with adenosine monophosphate and aminoimidazole carboxamide ribotide, respectively, and subsequent alkaline phosphatase-catalysed dephosphorylation of the resulting products.. The detection of SAICAr and SAdo in DBS was linear over the range of 0-25μmol/L. The respective intra-assay and inter-assay imprecision values were less than 10.7% and 15.2% for SAICAr and 4.7% and 5.7% for SAdo. The recoveries from DBS spiked with different concentrations of SAICAr and SAdo were between 94% and 117%. The concentrations of SAICAr and SAdo were higher in the archived DBS from dADSL patients (SAICAr, 0.03-4.7μmol/L; SAdo, 1.5-21.3μmol/L; n=5) compared to those of the control subjects (SAICAr, 0-0.026μmol/L; SAdo, 0.06-0.14μmol/L; n=31), even after DBSs from dADSL patients were stored for 2-23years.. We developed and validated a method of succinylpurine analysis in DBS that improves selective screening for dADSL in the paediatric population and may be used for retrospective diagnosis to aid the genetic counselling of affected families.

Topics: Adenosine; Adenylosuccinate Lyase; Aminoimidazole Carboxamide; Autistic Disorder; Carbon Isotopes; Chromatography, Liquid; Dried Blood Spot Testing; Humans; Infant, Newborn; Limit of Detection; Purine-Pyrimidine Metabolism, Inborn Errors; Reference Standards; Ribonucleosides; Tandem Mass Spectrometry

Adenylosuccinate lyase (ADSL) is a homotetrameric enzyme involved in the de novo purine biosynthesis pathway and purine nucleotide cycle. Missense mutations in the protein lead to ADSL deficiency, an inborn error of purine metabolism characterized by neurological and physiological symptoms. ADSL deficiency is biochemically diagnosed by elevated levels of succinylaminoimidazolecarboxamide riboside (SAICAr) and succinyladenosine (S-Ado), the dephosphorylated derivatives of the substrates. S-Ado/SAICAr ratios have been associated with three phenotypic groups. Different hypotheses to explain these ratios have been proposed. Recent studies have focused on measuring activity on the substrates independently. However, it is important to examine mixtures of the substrates to determine if mutations affect enzyme activity on both substrates similarly in these conditions. The two substrates may experience an indirect communication due to being acted upon by the same enzyme, altering their activities from the non-competitive case. In this study, we investigate this hidden coupling between the two substrates. We chose two mutations that represent extremes of the phenotype, R426H and R303C. We describe a novel electrochemical-detection method of measuring the kinetic activity of ADSL in solution with its two substrates at varying concentration ratios. Furthermore, we develop an enzyme kinetic model to predict substrate activity from a given ratio of substrate concentrations. Our findings indicate a non-linear dependence of the activities on the substrate ratios due to competitive binding, distinct differences in the behaviors of the different mutations, and S-Ado/SAICAr ratios in patients could be explained by inherent properties of the mutant enzyme.

Topics: Adenosine; Adenylosuccinate Lyase; Aminoimidazole Carboxamide; Autistic Disorder; Chromatography, High Pressure Liquid; Electrochemistry; Homozygote; Humans; Kinetics; Mutagenesis, Site-Directed; Mutation, Missense; Purine-Pyrimidine Metabolism, Inborn Errors; Ribonucleotides; Substrate Specificity

The aim of this study was to develop a high-throughput urine screening technique for adenylosuccinate lyase (ADSL) deficiency and to evaluate S-adenosyl-l-methionine (SAMe) as a potential treatment for this disorder.. Testing for succinyladenosine (S-Ado), a marker of ADSL deficiency, was incorporated into a screening panel for urine biomarkers for inborn errors of metabolism using electrospray tandem mass spectrometry. Liquid chromatography-mass spectrometry and high-performance liquid chromatography were used to confirm and monitor the response of metabolites to oral SAMe treatment.. Increased levels of S-Ado were detected in a 3-month-old male infant with hypotonia and seizures. ADSL gene sequencing revealed a previously described c.-49T>C mutation and a novel c.889_891dupAAT mutation, which was likely to disrupt enzyme function. After 9 months of SAMe treatment, there was no clear response evidenced in urine metabolite levels or clinical parameters.. These results demonstrate proof of the principle for the high-throughput urine screening technique, allowing earlier diagnosis of patients with ADSL deficiency. However, early treatment with SAMe does not appear to be effective in ADSL deficiency. It is suggested that although SAMe treatment may ameliorate purine nucleotide deficiency, it cannot correct metabolic syndromes in which a toxic nucleotide is present, in this case presumed to be succinylaminoimidazole carboxamide ribotide.

Topics: Adenosine; Adenylosuccinate Lyase; Administration, Oral; Autistic Disorder; Child, Preschool; Chromatography, Liquid; Electroencephalography; Genotype; High-Throughput Screening Assays; Humans; Longitudinal Studies; Male; Mutation; Purine-Pyrimidine Metabolism, Inborn Errors; S-Adenosylmethionine; Spectrometry, Mass, Electrospray Ionization

Adenylosuccinate lyase deficiency (dADSL) is a rare inherited metabolic disorder. Biochemical diagnosis of the disease is based on the determination of enormously elevated urinary levels of succinylaminoimidazole carboxamide riboside (SAICA-riboside) and succinyladenosine (SAdo). We report a case of false negative screening for dADSL caused by deribosylation of the urinary biomarkers SAICA-riboside and SAdo.. A thin-layer chromatography (TLC) method with Pauly reagent detection of SAICA-riboside was used as a screening method. High-performance liquid chromatography with diode-array detection (HPLC-DAD) and LC-MS/MS methods were used for the identification and quantitative determination of SAICA-riboside, SAdo, succinylaminoimidazole carboxamide (SAICA) and succinyladenine (SA).. Following a negative TLC screening in a known case of dADSL, we analyzed urine using HPLC-DAD. The concentration of SAICA-riboside was 2.7mmol/mol creatinine (below the TLC detection limit), and we detected the two abnormal metabolites identified by LC-MS/MS as SAICA and SA. We showed that SAICA and SA were produced by deribosylation of SAICA-riboside and SAdo in the patient's urine. Studies performed by monitoring the production of SAICA and SA after the addition of SAICA-riboside and SAdo to the patient's urine and to urine samples from patients with urinary tract infections suggested that deribosylation is facilitated by bacterial enzymes.. Screening methods for the diagnosis of dADSL may be falsely negative due to bacteria-mediated deribosylation of SAICA-riboside and SAdo. HPLC-DAD or LC-MS/MS analyses allowing for simultaneous detection of SAICA-riboside, SAdo and their deribosylation products SAICA and SA should be preferentially used for the diagnosis of dADSL in urine.

Topics: Adenosine; Adenylosuccinate Lyase; Aminoimidazole Carboxamide; Autistic Disorder; Bacterial Proteins; Child, Preschool; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Enterococcus faecalis; Enzymes; False Negative Reactions; Humans; Klebsiella pneumoniae; Purine-Pyrimidine Metabolism, Inborn Errors; Ribonucleosides; Tandem Mass Spectrometry; Urine

Adenylosuccinate lyase (ADSL) deficiency is a rare inborn error of metabolism resulting in accumulation of metabolites including succinylaminoimidazole carboxamide riboside (SAICAr) and succinyladenosine (S-Ado) in the brain and other tissues. Patients with ADSL have progressive psychomotor retardation, neonatal seizures, global developmental delay, hypotonia, and autistic features, although variable clinical manifestations may make the initial diagnosis challenging. Two cases of the severe form of the disease are reported here: an 18-month-old boy with global developmental delay, intractable neonatal seizures, progressive cerebral atrophy, and marked hypomyelination, and a 3-month-old girl presenting with microcephaly, neonatal seizures, and marked psychomotor retardation. In both patients in vivo proton magnetic resonance spectroscopy (MRS) showed the presence of S-Ado signal at 8.3 ppm, consistent with a prior report. Interestingly, SAICAr signal was also detectable at 7.5 ppm in affected white matter, which has not been reported in vivo before. A novel splice-site mutation, c.IVS12 + 1/G > C, in the ADSL gene was identified in the second patient. Our findings confirm the utility of in vivo proton MRS in suggesting a specific diagnosis of ADSL deficiency, and also demonstrate an additional in vivo resonance (7.5 ppm) of SAICAr in the cases of severe disease.

Topics: Adenosine; Adenylosuccinate Lyase; Aminoimidazole Carboxamide; Autistic Disorder; Brain; Developmental Disabilities; DNA Mutational Analysis; Female; Humans; Image Enhancement; Image Interpretation, Computer-Assisted; Infant; Magnetic Resonance Spectroscopy; Male; Psychomotor Disorders; Purine-Pyrimidine Metabolism, Inborn Errors; Ribonucleosides

Most cases of adenylosuccinate lyase (ADSL OMIM 103050) deficiency reported to date are confined to the various European ethnic groups. We report on the first Malaysian case of ADSL deficiency, which appears also to be the first reported Asian case. The case was diagnosed among a cohort of 450 patients with clinical features of psychomotor retardation, global developmental delay, seizures, microcephaly and/or autistic behaviour. The patient presented with frequent convulsions and severe myoclonic jerk within the first few days of life and severe psychomotor retardation. The high performance liquid chromatography (HPLC) profile of the urine revealed the characteristic biochemical markers of succinyladenosine (S-Ado) and succinyl-aminoimidazole carboximide riboside (SAICAr). The urinary S-Ado/SAICAr ratio was found to be 1.02 (type I ADSL deficiency). The patient was compound heterozygous for two novel mutations, c.445C > G (p.R149G) and c.774_778insG (p.A260GfsX24).

Topics: Adenosine; Adenosine Monophosphate; Adenylosuccinate Lyase; Aminoimidazole Carboxamide; Autistic Disorder; Biomarkers; Child Development; Chromatography, High Pressure Liquid; DNA Mutational Analysis; Genetic Predisposition to Disease; Genetic Testing; Heterozygote; Humans; Infant; Infant, Newborn; Malaysia; Male; Mutation; Myoclonus; Phenotype; Predictive Value of Tests; Psychomotor Disorders; Psychomotor Performance; Purine-Pyrimidine Metabolism, Inborn Errors; Ribonucleosides; Seizures; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry

Adenylosuccinate lyase deficiency is a rare autosomal disorder of de novo purine synthesis, which results in the accumulation of succinylpurines in body fluids. Patients with adenylosuccinate lyase deficiency show a variable combination of mental retardation, epilepsy and autistic features and are usually discovered during screens for unexplained encephalopathy using the Bratton-Marshall assay that reveals the excretion of the succinylaminoimidazolecarboxamide riboside (SAICAr). Here, we report on two sisters aged 11 and 12 years presented with global developmental delay, motor apraxia, severe speech deficits, seizures and behavioural features, which combined excessive laughter, a very happy disposition, hyperactivity, a short attention span, the mouthing of objects, tantrums and stereotyped movements that gave a behavioural profile mimicking Angelman syndrome. Both patients had an increased succinyladenosine/SAICAr ratio of 1.6, and exhibited a novel homozygous missense mutation (c.674T>C; p.Met225Thr) in the exon 6 of the ADSL gene. We suggest that these clinical features might be a new presentation of adenylosuccinate lyase deficiency. On the basis of this observation, although adenylosuccinate lyase deficiency is a rare disorder, this diagnosis should be considered in patients with mental retardation and a behavioural profile suggestive of Angelman syndrome.

Topics: Adenosine; Adenylosuccinate Lyase; Aminoimidazole Carboxamide; Angelman Syndrome; Behavior; Child; Chromatography, High Pressure Liquid; Consanguinity; Female; Humans; Intellectual Disability; Mutation, Missense; Pedigree; Phenotype; Purine-Pyrimidine Metabolism, Inborn Errors; Ribonucleotides; Sequence Analysis, DNA; Stereotyped Behavior

Deficiency of adenylosuccinate lyase (ADSL) (OMIM 103050) is an autosomal recessive disorder of the purine de novo synthesis pathway and purine nucleotide cycle, diagnosed so far in approximately 50 patients. The clinical presentation is characterized by severe neurological involvement including hypotonia, seizures, developmental delay and autistic features. Epilepsy in ADSL deficiency is frequent and occurs in approximately two-thirds of patients, beginning either early in the neonatal period or after the first year of life. At present there is no treatment of proven clinical efficacy. Despite of the increasing number of ADSL-deficient patients reported, there are only a few communications of therapeutic considerations or efforts. Among them only two showed some beneficial effects in ADSL-deficient patients. D-ribose, a simple and relatively cheap therapy, has been associated with improvement of behaviour and progressive reduction of the seizure frequency in one 13-year-old patient with ADSL deficiency. In this study we have re-examined D-ribose treatment in four ADSL-deficient patients. Assessments consisted of biochemical markers and neurological outcome. The 12-month trial of D-ribose failed to show any clinical benefit in ADSL patients with both milder and severe phenotype. D-ribose administration was accompanied by neither reduction in seizure frequency nor growth enhancement. Additionally, patients with milder type II presented the first seizure after 4 and 8 months of the D-ribose treatment. Therefore, we could not confirm a positive effect of D-ribose as previously reported.

Topics: Adenosine; Adenylosuccinate Lyase; Aminoimidazole Carboxamide; Autistic Disorder; Blood Glucose; Child; Child, Preschool; Creatinine; Female; Growth Disorders; Humans; Poland; Purine-Pyrimidine Metabolism, Inborn Errors; Ribonucleosides; Ribose; Seizures; Severity of Illness Index; Treatment Failure; Uric Acid

Adenylosuccinase (ADSL) deficiency is an autosomal recessive disorder affecting mainly the nervous system. The disease causes psychomotor retardation, frequently with autistic features and epilepsy. ADSL deficiency may be diagnosed by detection of two abnormal metabolites in body fluids--succinyladenosine (S-Ado) and succinylaminoimidazole carboxamide riboside (SAICAr). It is assumed that the former metabolite is neurotoxic. We present clinical, biochemical and neuropathological findings of a child affected by a severe form of ADSL deficiency. She had progressive neurological symptoms that started immediately after birth and died at 2.5 months of age. Macroscopically the brain showed signs of moderate atrophy. Histological examination of all grey matter structures showed widespread damage of neurons accompanied by microspongiosis of neuropile. Cerebral white matter showed lack of myelination in the centrum semiovale and diffuse spongiosis of neuropile. Myelination appropriate for the age was visible in posterior limb of internal capsule, in striatum, thalamus and in brain stem structures but diffuse destruction of myelin sheets was seen with severe marked astroglial reaction with signs of destruction of the cells and their processes. Ultrastructural examination showed enormous destruction of all cellular elements, but astonishingly mitochondria were relatively spared. The neuropathological changes can be considered as the neurotoxic result of metabolic disturbances connected with adenylosuccinase deficiency.

Topics: Adenosine; Adenylosuccinate Lyase; Aminoimidazole Carboxamide; Brain; Brain Diseases, Metabolic, Inborn; Female; Humans; Infant; Infant, Newborn; Poland; Purine-Pyrimidine Metabolism, Inborn Errors; Ribonucleosides

The enzyme adenylosuccinate lyase (ADSL) intervenes twice in the biosynthesis of adenine nucleotides. ADSL deficiency is an inherited metabolic disease characterized by various degrees of psychomotor retardation and accumulation of dephosphorylated enzyme substrates 5-amino-4-imidazole-N-succinocarboxamide riboside (SAICAr) and succinyladenosine (SAdo) in body fluids. Severity of symptoms seems to correlate with residual activity of mutant enzyme and with SAdo/SAICAr concentration ratio in cerebrospinal fluid. To better understand the pathogenetic mechanisms of the disease symptoms, studies of catalytic properties of mutant enzymes together with in vitro and in vivo experiments utilizing SAICAr and SAdo must be performed. Such studies require availability of both ADSL substrates, 5-amino-4-imidazole-N-succinocarboxamide ribotide (SAICAR) and succinyladenosine 5'-monophosphate (SAMP) and their dephosphorylated products in sufficient amounts and purity. Except for SAMP, none of these compounds is commercially available and they must therefore be synthesized. SAICAR was prepared by recombinant human ADSL-catalysed reaction of AICAR (5-aminoimidazole-4-carboxamide) with fumarate and isolated by thin-layer chromatography. SAICAr and SAdo were prepared by calf intestine alkaline phosphatase-catalysed dephosphorylation of SAICAR and SAMP and isolated on cation- and anion-exchange resin columns. The procedures described are easily scalable and provide high yields of sufficiently pure products for use in experiments related to studies of pathogenetic mechanisms in ADSL deficiency.

Topics: Adenosine; Adenylosuccinate Lyase; Aminoimidazole Carboxamide; Biochemistry; Cations; Chemistry, Clinical; Chromatography, High Pressure Liquid; Chromatography, Ion Exchange; Cloning, Molecular; DNA, Complementary; Humans; Mutation; Phosphorylation; Purine-Pyrimidine Metabolism, Inborn Errors; Recombinant Proteins; Ribonucleotides; Substrate Specificity; Time Factors

A deficiency of adenylosuccinate lyase (ASDL) is characterised by the accumulation of SAICAriboside (SAICAr) and succinyladenosine (S-Ado) in body fluids. The severity of the clinical presentation correlates with a low S-Ado/SAICAr ratio in body fluids. We report the first British case of ADSL deficiency. The patient presented at 14 days with a progressive neonatal encephalopathy and seizures. There was marked axial and peripheral hypotonia. Brain MRI showed widespread white matter changes. She died at 4 weeks of age. Concentrations of SAICAr and SAdo were markedly elevated in urine, plasma and CSF and the SAdo/SAICAr ratio was low, consistent with the severe phenotype. The patient was compound heterozygous for 2 novel ADSL mutations; c.9 G>C (A3P) and c.572 C>T (R190X).

Topics: Adenosine; Adenylosuccinate Lyase; Aminoimidazole Carboxamide; Catalysis; Exons; Fatal Outcome; Female; Heterozygote; Humans; Infant, Newborn; Mutation; Phenotype; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Ribonucleotides

Succinyladenosine (S-Ado) is a biochemical marker of adenylosuccinase deficiency--the genetic defect of purine de novo synthesis. S-Ado has been previously reported as normally undetectable in cerebrospinal fluid (CSF) of children not suffering from this defect. In present study, we employed solid-phase extraction and thin-layer chromatography for isolation of a compound with spectral and chromatographic characteristics identical to S-Ado from human CSF. The high-performance liquid chromatography-negative-ion electrospray ionization mass spectrometry analysis confirmed that the isolated compound is S-Ado. We established the reference values of S-Ado in CSF of children (1.1+/-0.4 micromol/l; mean +/- S.D; n = 26) by means of reversed-phase HPLC method on a C18 column with UV detection.

Topics: Adenosine; Child; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Humans; Mass Spectrometry; Purine-Pyrimidine Metabolism, Inborn Errors; Reference Standards; Reproducibility of Results; Spectrophotometry, Ultraviolet

We report a male infant with adenylosuccinase deficiency who developed epileptic seizures on the second day of life. Growth was normal and seizures were well controlled with anti-epileptic drugs. Despite axial hypotonia associated with peripheral hypertonicity he presented some development until seven months of age, when he developed high fever and died within a few hours. Although clinical heterogeneity in this disorder of purine synthesis and interconversion is well-known, in 14 out of 17 cases who experienced epilepsy seizures started after the first year of life. The early presentation in our index patient followed by his sudden death at the age of 7 months has not been described before. A search for disorders of purine metabolism should be included in the screening programme for every child with severe neonatal convulsions.

Topics: Adenosine; Adenylosuccinate Lyase; Aminoimidazole Carboxamide; Anticonvulsants; Death, Sudden; Epilepsy; Humans; Infant, Newborn; Male; Purine-Pyrimidine Metabolism, Inborn Errors; Ribonucleotides

An automated screening system for purine and pyrimidine metabolism disorders using high-performance liquid chromatography (HPLC) with column switching is described. The system consists of a reversed-phase column, a cation-exchange column, a column switch, four sets of ultraviolet absorbance detectors, a microcomputer and other conventional equipment. As this system permits the simultaneous determination of urinary orotic acid, uracil, dihydrouracil, pseudouridine, xanthine, 2,8-dihydroxyadenine and succinyladenosine, it offers a useful method for the detection of orotic aciduria, dihydropyrimidine dehydrogenase deficiency, dihydropyrimidinuria, xanthinuria, adenine phosphoribosyltransferase deficiency and adenylosuccinase deficiency.

Topics: Adenine; Adenosine; Autoanalysis; Chromatography, High Pressure Liquid; Humans; Orotic Acid; Pseudouridine; Purine-Pyrimidine Metabolism, Inborn Errors; Uracil; Xanthine; Xanthines

Patients with inherited adenylosuccinase deficiency excrete large quantities of succinyloaminoimidazolecarboxamide riboside (SAICAR) and succinyloadenosine (SAdo). A two-dimensional thin-layer chromatography method for the detection of SAICAR is described. The method consists of isolation of imidazoles with a cation exchange resin; TLC on cellulose plates, solvent I, isopropanol-ammonia 10% (4:1) and II, butanol-acetic acid-water (4:1:1); detection with Pauly reagent. SAICAR gives rise to an isolated spot with a characteristic bluish color. Also a simple one-dimensional thin-layer chromatography method using urine without any pretreatment for screening of high risk populations is given. Four new cases could be diagnosed. Clinical and chemical data, including concentrations of SAICAR and SAdo in urine, plasma and cerebrospinal fluid, determined by cation exchange column chromatography, are presented.

Topics: Adenosine; Adenylosuccinate Lyase; Adolescent; Aminoimidazole Carboxamide; Autoanalysis; Child; Chromatography, Ion Exchange; Chromatography, Thin Layer; Erythrocytes; Female; Humans; Imidazoles; Infant; Lyases; Male; Purine-Pyrimidine Metabolism, Inborn Errors; Purines; Ribonucleosides; Uric Acid

Patients with inherited adenylosuccinase deficiency excrete large quantities of succinyloaminoimidazolecarboxamide riboside (SAICAR) and succinyloadenosine (SAdo). A two dimensional thin layer chromatography method for the detection of SAICAR is described. The method consists of 1: isolation of imidazoles with a cation exchange resin; 2: tlc on cellulose plates, solvent I: isopropanol-ammonia 10% (4:1) and II: butanol-acetic acid-water (4:1:1); detection with Pauly reagent. SAICAR gives rise to an isolated spot with a characteristic bluish color. Also a simple one dimensional thin layer chromatography method for screening of high risk populations is given. Four new cases could be diagnosed. Clinical and chemical data, including concentrations of SAICAR and SAdo in urine, plasma and cerebrospinal fluid, determined by column chromatography, are presented.

Topics: Adenosine; Adenylosuccinate Lyase; Aminoimidazole Carboxamide; Child; Chromatography, Thin Layer; Female; Humans; Infant; Infant, Newborn; Lyases; Male; Purine-Pyrimidine Metabolism, Inborn Errors; Ribonucleosides

The Bratton-Marshall reaction can be used to identify patients with adenylosuccinate lyase deficiency. These patients excrete in their urine the dephosphorylated derivative of the de novo purine synthesis intermediate 5'-phosphoribosyl-4-(N-succinylcarboxamide)-5-aminoimidazole (SAICAR). The test described here depends on a coupling reaction of N-1-naphthylethylenediamine with diazotized ribosyl-4-(N-succinylcarboxamide)-5-aminoimidazole giving rise to a fast developing purple chromaphore with a maximum absorbance at 555 nm. Using the closely related compound ribosyl-5-amino-4-imidazolecarboxamide (AICA riboside) as a standard, concentrations as low as 1.0 microM produce a visible color change. The absorption at 555 nM of the azo compound increases as a linear function of the concentration of AICA riboside in the reaction. The use of a filter-paper dipstick for urine sampling and storage is also described. The two metabolites which are present in increased concentration in biological fluids of adenylosuccinate lyase deficient patients are stable on the dipstick for at least 60 days when stored at room temperature (25 degrees C).

Topics: Adenosine; Adenylosuccinate Lyase; Aminoimidazole Carboxamide; Autistic Disorder; Chromatography, High Pressure Liquid; Creatinine; Ethylenediamines; Humans; Imidazoles; Lyases; Purine-Pyrimidine Metabolism, Inborn Errors; Reagent Strips; Ribonucleosides; Ribonucleotides; Spectrophotometry