Evidence map›Paper›PMID 31304092›Full record

ArticleMolecular genetics and metabolism reports2019

A longitudinal study of neurocognition and behavior in patients with Hurler-Scheie syndrome heterozygous for the L238Q mutation.

Alia Ahmed, Li Ou, Kyle Rudser, Elsa Shapiro, Julie B Eisengart, Kelly King, Agnes Chen, Patricia Dickson, Chester B Whitley

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

Article in Molecular genetics and metabolism reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.4field-weighted citation impact, top 36% 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

1 citing paper in PubMed, 4 citations in OpenAlex.

  1. Article
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

9 authors at 3 institutions in 1 country.

Alia AhmedDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
Li OuGene Therapy Center, Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
Kyle RudserDivision of Biostatistics, University of Minnesota, Minneapolis, MN 55455, USA.
Elsa ShapiroDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
Julie B EisengartDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
Kelly KingDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
Agnes ChenDepartment of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
Patricia DicksonDepartment of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
Chester B WhitleyDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
University of Minnesota · USHarbor–UCLA Medical Center · USUCLA Medical Center · US

Funding

The Impact of COVID-19 on People Living with Rare Diseases and Their FamiliesU2CTR002818 · NCATS · CINCINNATI CHILDRENS HOSP MED CTR · PI Maurizio Macaluso · 2019 to 2026
$51.2M
Training & EducationU54NS065768 · NINDS · UNIVERSITY OF MINNESOTA · PI WHITLEY, CHESTER B. · 2009 to 2024
$17.7M
NCATS NIH HHS U2C TR002818NINDS NIH HHS U54 NS065768
6 · The paper itself

Abstract

Previous research has demonstrated the mutation, c.712T>A (p.L238Q) of the gene for α-L- iduronidase (IDUA) in patients with Hurler-Scheie syndrome is relatively severe when paired with a nonsense or deletion or splice-site mutation. This mutation was also found to be associated with psychiatric symptoms. This research presents longitudinal data and protein analysis to further investigate the severity and natural history of these unique patients.

methodsSix patients heterozygous for L238Q were compared to six patients with Hurler-Scheie without the L238Q mutations. Somatic burden of disease, IQ, memory, attention, adaptive functioning and behavioral measures were given yearly over 2 to 4 years from 2009 to 2014. The impact of L238Q on the IDUA enzyme was examined using 7 bioinformatics tools and a 3D structural analysis.

resultsSimilar to the cross sectional study, the L238Q patients had more severe abnormalities in IQ, attention, adaptive functioning, and behavioral functioning than the comparison group. There were no major differences between the two groups in change over time; IQ for both groups was stable with some behavioral areas showing improvement. Over time, both groups declined in visual spatial memory and, attention/visual processing. They also showed increased anxiety. Structural and bioinformatics analysis of the L238Q suggest that this mutation causes a significant reduction in the IDUA enzyme's potential catalytic activity, and this mutation may be more severe than other mutations contributing to the Hurler-Scheie syndrome phenotype, presumably causing the psychiatric disease.

conclusionL238Q patients demonstrate severe neurocognitive and neurobehavioral deficits but are relatively stable. Like the comparison group, decreasing visual spatial memory and attention and increasing anxiety suggest more intervention in life skills and emotional social supports are needed.

Indexed as

Hurler-Scheie syndromeL238Q mutationMucopolysaccharidosis (MPS)Neurocognitionα-L-iduronidase

Identifiers

PMID31304092
PMCPMC6603334
OpenAlexW2955380678

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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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.