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New biomarkers for early diagnosis of Lesch-Nyhan disease revealed by metabolic analysis on a large cohort of patients

Overview of attention for article published in Orphanet Journal of Rare Diseases, January 2015
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  • High Attention Score compared to outputs of the same age and source (81st percentile)

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1 patent

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Title
New biomarkers for early diagnosis of Lesch-Nyhan disease revealed by metabolic analysis on a large cohort of patients
Published in
Orphanet Journal of Rare Diseases, January 2015
DOI 10.1186/s13023-014-0219-0
Pubmed ID
Authors

Irène Ceballos-Picot, Aurélia Le Dantec, Anaïs Brassier, Jean-Philippe Jaïs, Morgan Ledroit, Julie Cahu, Hang-Korng Ea, Bertrand Daignan-Fornier, Benoît Pinson

Abstract

BackgroundLesch-Nyhan disease is a rare X-linked neurodevelopemental metabolic disorder caused by a wide variety of mutations in the HPRT1 gene leading to a deficiency of the purine recycling enzyme hypoxanthine-guanine phosphoribosyltransferase (HGprt). The residual HGprt activity correlates with the various phenotypes of Lesch-Nyhan (LN) patients and in particular with the different degree of neurobehavioral disturbances. The prevalence of this disease is considered to be underestimated due to large heterogeneity of its clinical symptoms and the difficulty of diagnosing of the less severe forms of the disease. We therefore searched for metabolic changes that would facilitate an early diagnosis and give potential clues on the disease pathogenesis and potential therapeutic approaches.MethodsLesch-Nyhan patients were diagnosed using HGprt enzymatic assay in red blood cells and identification of the causal HPRT1 gene mutations. These patients were subsequently classified into the three main phenotypic subgroups ranging from patients with only hyperuricemia to individuals presenting motor dysfunction, cognitive disability and self-injurious behavior. Metabolites from the three classes of patients were analyzed and quantified by High Performance Ionic Chromatography and biomarkers of HGprt deficiency were then validated by statistical analyses.ResultsA cohort of 139 patients, from 112 families, diagnosed using HGprt enzymatic assay in red blood cells, was studied. 98 displayed LN full phenotype (86 families) and 41 (26 families) had attenuated clinical phenotypes. Genotype/phenotype correlations show that LN full phenotype was correlated to genetic alterations resulting in null enzyme function, while variant phenotypes are often associated with missense mutations allowing some residual HGprt activity. Analysis of metabolites extracted from red blood cells from 56 LN patients revealed strong variations specific to HGprt deficiency for six metabolites (AICAR mono- and tri-phosphate, nicotinamide, nicotinic acid, ATP and Succinyl-AMP) as compared to controls including hyperuricemic patients without HGprt deficiency.ConclusionsA highly significant correlation between six metabolites and the HGprt deficiency was established, each of them providing an easily measurable marker of the disease. Their combination strongly increases the probability of an early and reliable diagnosis for HGprt deficiency.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 63 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 63 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 10 16%
Student > Bachelor 9 14%
Student > Postgraduate 7 11%
Student > Master 7 11%
Student > Doctoral Student 5 8%
Other 11 17%
Unknown 14 22%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 16 25%
Medicine and Dentistry 14 22%
Agricultural and Biological Sciences 5 8%
Psychology 5 8%
Pharmacology, Toxicology and Pharmaceutical Science 2 3%
Other 5 8%
Unknown 16 25%

Attention Score in Context

This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 15 February 2018.
All research outputs
#3,397,459
of 12,510,237 outputs
Outputs from Orphanet Journal of Rare Diseases
#477
of 1,367 outputs
Outputs of similar age
#70,841
of 271,015 outputs
Outputs of similar age from Orphanet Journal of Rare Diseases
#7
of 44 outputs
Altmetric has tracked 12,510,237 research outputs across all sources so far. This one has received more attention than most of these and is in the 72nd percentile.
So far Altmetric has tracked 1,367 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.0. This one has gotten more attention than average, scoring higher than 63% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 271,015 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 73% of its contemporaries.
We're also able to compare this research output to 44 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 81% of its contemporaries.