Evidence map›Paper›PMID 25481104›Full record

ArticleMolecular genetics and metabolism2015

Clinical severity in Lesch-Nyhan disease: the role of residual enzyme and compensatory pathways.

Rong Fu, Diane Sutcliffe, Hong Zhao, Xinyi Huang, David J Schretlen, Steve Benkovic, H A Jinnah

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular genetics and metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
1.4field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

48 citing papers in PubMed, 92 citations in OpenAlex.

  1. A new conditional mouse model for Cre-mediated restoration ofbioRxiv : the preprint server for biology · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Rong FuDepartment of Neurology, Emory University, Atlanta, GA, USA.
Diane SutcliffeDepartment of Neurology, Emory University, Atlanta, GA, USA; Department of Human Genetics, Emory University, Atlanta, GA, USA; Department of Pediatrics, Emory University, Atlanta, GA, USA.
Hong ZhaoDepartment of Chemistry, Pennsylvania State University, University Park, PA, USA.
Xinyi HuangDepartment of Chemistry, Pennsylvania State University, University Park, PA, USA.
David J SchretlenDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Steve BenkovicDepartment of Chemistry, Pennsylvania State University, University Park, PA, USA.
H A JinnahDepartment of Neurology, Emory University, Atlanta, GA, USA; Department of Human Genetics, Emory University, Atlanta, GA, USA; Department of Pediatrics, Emory University, Atlanta, GA, USA. Electronic address: hjinnah@emory.edu.
Emory University · USPennsylvania State University · USJohns Hopkins University · US

Funding

TRANSFORMYLASE ENZYMES--DIHYDROFOLATE REDUCTASER01GM024129 · NIGMS · PENNSYLVANIA STATE UNIVERSITY-UNIV PARK · PI BENKOVIC, STEPHEN J · 1985 to 2024
$5.2M
Lesch-Nyhan Disease: Neuroanatomic and Biochemical Bases of the PhenotypeR01HD053312 · NICHD · JOHNS HOPKINS UNIVERSITY · PI SCHRETLEN, DAVID J · 2008 to 2011
$2.0M
TRANSFORMYLASE ENZYMES/DIHYDROFOLATE REDUCTASER37GM024129 · NIGMS · PENNSYLVANIA STATE UNIVERSITY-UNIV PARK · PI BENKOVIC, STEPHEN J · 1987 to 1996
–
NICHD NIH HHS HD 053312NICHD NIH HHS R01 HD053312NIGMS NIH HHS GM024129NIGMS NIH HHS R01 GM024129NIGMS NIH HHS R37 GM024129
6 · The paper itself

Abstract

Mutations in the HPRT1 gene, which encodes the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HGprt), cause Lesch-Nyhan disease (LND) and more mildly affected Lesch-Nyhan variants. Prior studies have suggested a strong correlation between residual hypoxanthine recycling activity and disease severity. However, the relevance of guanine recycling and compensatory changes in the de novo synthesis of purines has received little attention. In the current studies, fibroblast cultures were established for 21 healthy controls and 36 patients with a broad spectrum of disease severity related to HGprt deficiency. We assessed hypoxanthine recycling, guanine recycling, steady-state purine pools, and de novo purine synthesis. There was a strong correlation between disease severity and either hypoxanthine or guanine recycling. Intracellular purines were normal in the HGprt-deficient fibroblasts, but purine wasting was evident as increased purine metabolites excreted from the cells. The normal intracellular purines in the HGprt-deficient fibroblasts were likely due in part to a compensatory increase in purine synthesis, as demonstrated by a significant increase in purinosomes. However, the increase in purine synthesis did not appear to correlate with disease severity. These results refine our understanding of the potential sources of phenotypic heterogeneity in LND and its variants.

Indexed as

Cells, CulturedFibroblastsGuanineHumansHypoxanthineHypoxanthine PhosphoribosyltransferaseLesch-Nyhan SyndromePurinesGuanineHypoxanthineHypoxanthine PhosphoribosyltransferasePurinesGenotype–phenotype correlationInherited metabolic diseasePurine metabolismPurinosome

Identifiers

PMID25481104
PMCPMC4277921
OpenAlexW2024390232

What OpenQuestion holds

Textmetadata
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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.