Clinical, biochemical and molecular findings in seven Polish patients with adenylosuccinate lyase deficiency

Jurecka, Agnieszka; Zikánová, Marie; Tylki‐Szymańska, Anna; Krijt, Jakub; Bogdańska, Anna; Gradowska, Wanda; Mullerova, K.; Sykut-Cegielska, Jolanta; Kmoch, Stanislav; Pronicka, Ewa

doi:10.1016/j.ymgme.2008.04.013

Cited by 64 publications

(72 citation statements)

References 28 publications

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“…Clinical, biochemical, and molecular data on ADSL patients were available to us either from our previous studies [Jurecka et al, 2008;Kmoch et al, 2000;Mouchegh et al, 2007] or compiled from the literature and existing databases (http://www.icp.ucl.ac.be/adsldb). The nucleotide numbering corresponds to the cDNA sequence deposited in GenBank under accession AF067853.1.…”

Section: Selection Of Adsl Phenotypes and Related Mutationsmentioning

confidence: 99%

“…The expression vectors pMAL-c2wtADSL and pMAL-c2 with ADSL mutants c.69C4G (p.Ser23Arg), c.340T4C (p.Tyr114His), [Jurecka et al, 2008;Kmoch et al, 2000;Mouchegh et al, 2007]. We introduced the mutations c.240A4C (p.Glu80Asp), c.261T4G (p.Asp87Glu), c.907C4T (p.Arg303Cys), c.1187G4A (p.Arg396His), and c.1349C4G (p.Thr450Ser) into the pMAL-c2w-tADSL vector using site-directed mutagenesis with mutation specific oligonucleotide primers and the GeneTailor TM SiteDirected Mutagenesis System Kit (Invitrogen, Paisley, UK).…”

Section: Preparation Of Ampicillin-resistant Adsl Expression Vectorsmentioning

confidence: 99%

“…We assigned individual patients into three main phenotypic groups according to the severity of their clinical presentation and S-Ado/SAICAr ratio value in cerebrospinal fluid or urine when the former was not available. From this cohort we selected 16 genotypes representing the neonatal fatal form (five cases), the severe childhood form (five cases), and the moderate or mild form (six cases) as defined by the corresponding clinical presentation and different S-Ado/SAICAr ratios [Jurecka et al, 2008;Kmoch et al, 2000;Mouchegh et al, 2007;Race et al, 2000;Sivendran et al, 2004]. In the selection process, we preferentially chose genotypes of patients diagnosed and characterized in our institute and recurrently observed genotypes.…”

Section: Selection Of Phenotypes and Mutationsmentioning

confidence: 99%

“…To date, about 60 patients with ADSL deficiency and 45 different disease-causing ADSL mutations have been reported [Gitiaux et al, 2009;Jurecka et al, 2008;Mouchegh et al, 2007;Spiegel et al, 2006]. Enzyme deficiency leads to the intracellular accumulation of SAICAR and S-AMP, which are consequently dephosphorylated intracellularly to SAICA-riboside (SAICAr) and succinyladenosine (S-Ado), respectively ( Fig.…”

Section: Introductionmentioning

confidence: 99%

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Biochemical and structural analysis of 14 mutant adsl enzyme complexes and correlation to phenotypic heterogeneity of adenylosuccinate lyase deficiency

et al. 2010

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Adenylosuccinate lyase (ADSL) deficiency is neurometabolic disease characterized by accumulation of dephosphorylated enzyme substrates SAICA-riboside (SAICAr) and succinyladenosine (S-Ado) in body fluids of affected individuals. The phenotypic severity differs considerably among patients: neonatal fatal, severe childhood, and moderate phenotypic forms correlating with different values for the ratio between S-Ado and SAICAr concentrations in cerebrospinal fluid have been distinguished. To reveal the biochemical and structural basis for this phenotypic heterogeneity, we expressed and characterized 19 ADSL mutant proteins identified in 16 patients representing clinically distinct subgroups. Respecting compound heterozygosity and considering the homotetrameric structure of ADSL, we used intersubunit complementation and prepared and characterized genotype-specific heteromeric mutant ADSL complexes. We correlated clinical phenotypes with biochemical properties of the mutant proteins and predicted structural impacts of the mutations. We found that phenotypic severity in ADSL deficiency is correlated with residual enzymatic activity and structural stability of the corresponding mutant ADSL complexes and does not seem to result from genotype-specific disproportional catalytic activities toward one of the enzyme substrates. This suggests that the S-Ado/SAICAr ratio is probably not predictive of phenotype severity; rather, it may be secondary to the degree of the patient's development (i.e., to the age of the patient at the time of sample collection).

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Section: Selection Of Adsl Phenotypes and Related Mutationsmentioning

confidence: 99%

Section: Preparation Of Ampicillin-resistant Adsl Expression Vectorsmentioning

confidence: 99%

Section: Selection Of Phenotypes and Mutationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Biochemical and structural analysis of 14 mutant adsl enzyme complexes and correlation to phenotypic heterogeneity of adenylosuccinate lyase deficiency

et al. 2010

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“…Using blood as a cell source of iPSCs cells has two major advantages, one is the blood is the easiest, most accessible source of cells, and second blood collection and storage is a well-established part of the medical system [38]. Among all the blood cells, only white blood cells (T cells and few myeloid cells) can be converted to iPS cells.…”

Section: Clinical Trial With Induced Pluripotent Stem Cells Ipscs Impmentioning

confidence: 99%

Induced pluripotent stem cells: An update

Singh

Bhoria

2015

Int J Blood Transfus Immunohematol

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AICAr to SAICAr ratio can serve as additional marker of AICAr use

Sobolevsky¹,

Piper

Ahrens³

et al. 2022

Drug Testing and Analysis

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AICAr (5‐aminoimidazole‐4‐carboxamide‐1‐β‐D‐ribofuranoside, commonly referred to as AICAR) is an adenosine monophosphate‐activated protein kinase agonist previously investigated for its therapeutic potential which has been shown to improve exercise performance in laboratory animals. For this reason, the World Anti‐Doping Agency prohibits the use of AICAr in sports. AICAr can easily be detected by means of liquid chromatography–mass spectrometry, but being an endogenous metabolite, it cannot be discriminated from AICAr of a non‐natural origin. Population‐based concentration thresholds have been suggested as a means to identify suspicious samples that would require further analysis by carbon isotope ratio mass spectrometry (CIR); however, it remains at the discretion of the laboratory how to apply them. Here, the urinary ratio of AICAr to SAICA‐riboside (SAICAr) that is a closely related purine metabolite was investigated. In an athlete population of 5517 samples, this ratio was relatively narrowly distributed with median values and 99th percentiles of 3.3 and 9.3, and 4.2 and 14 in male and female athletes, respectively. Analysis of urine samples obtained from an AICAr administration study demonstrated that the AICAr/SAICAr ratio can serve in addition to AICAr concentration as a valuable diagnostic trigger for follow‐up analysis by CIR. Conceivably, this combination can offer better retrospectivity than AICAr concentration alone by allowing to decrease the AICAr concentration threshold without significantly increasing the number of suspicious samples.

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Clinical, biochemical and molecular findings in seven Polish patients with adenylosuccinate lyase deficiency

Cited by 64 publications

References 28 publications

Biochemical and structural analysis of 14 mutant adsl enzyme complexes and correlation to phenotypic heterogeneity of adenylosuccinate lyase deficiency

Biochemical and structural analysis of 14 mutant adsl enzyme complexes and correlation to phenotypic heterogeneity of adenylosuccinate lyase deficiency

Induced pluripotent stem cells: An update

AICAr to SAICAr ratio can serve as additional marker of AICAr use

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