Evidence map›Paper›PMID 42187043›Full record

ArticleDisease models & mechanisms2026

A model of free sialic acid storage disorder reveals hypomyelinating leukodystrophy and Purkinje cell degeneration.

Mary E Hackbarth, Mahin S Hossain, Marya S Sabir, Petcharat Leoyklang, Heidi Dorward, John Douglas Burke, Gene Elliot, Lisa Garrett, Patricia Zerfas, Danielle A Springer and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Disease models & mechanisms, 2026. 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
–field-weighted citation impact
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.

  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

15 authors.

Mary E HackbarthUDP Translational Laboratory, NIH Undiagnosed Diseases Program, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0003-1325-3165
Mahin S HossainHuman Biochemical Genetics Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0009-0009-4539-1504
Marya S SabirUDP Translational Laboratory, NIH Undiagnosed Diseases Program, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0001-6333-4049
Petcharat LeoyklangUDP Translational Laboratory, NIH Undiagnosed Diseases Program, National Institutes of Health, Bethesda, MD 20892, USA.
Heidi DorwardHuman Biochemical Genetics Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
John Douglas BurkeHuman Biochemical Genetics Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Gene ElliotEmbryonic Stem Cell and Transgenic Mouse Core, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Lisa GarrettEmbryonic Stem Cell and Transgenic Mouse Core, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Patricia ZerfasDiagnostic and Research Services Branch, Office of Research Services, National Institutes of Health, Bethesda, MD 20892, USA.
Danielle A SpringerMurine Phenotyping Core, National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA.
Laura PollardBiochemical Genetics Laboratory, Greenwood Genetic Center, Greenwood, SC 29646, USA.ORCID 0000-0002-8359-6369
Stephen WincovitchAdvanced Imaging and Analysis Core, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0002-5820-0174
Marjan HuizingHuman Biochemical Genetics Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0002-9375-9539
William A GahlUDP Translational Laboratory, NIH Undiagnosed Diseases Program, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0002-2494-6752
May Christine V MalicdanUDP Translational Laboratory, NIH Undiagnosed Diseases Program, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0003-1697-6959

Funding

Intramural Research ProgramNHGRI NIH HHS Intramural Research ProgramNIH HHSNIH Intramural Research ProgramSalla Treatment and Research Foundation
6 · The paper itself

Abstract

Free sialic acid storage disorder (FSASD) is a rare, neurodegenerative, lysosomal storage disease caused by biallelic variants in SLC17A5, which encodes the lysosomal sialic acid exporter, sialin. Although clinical severity varies, all affected individuals exhibit progressive neurological decline and characteristic lysosomal and urinary accumulation of free sialic acid. No US Food and Drug Administration-approved therapies currently exist, and the molecular underpinnings of central nervous system (CNS) dysfunction remain poorly defined. To model the most prevalent FSASD-associated allele, we generated a Slc17a5R39C mouse model carrying the pathogenic p.Arg39Cys variant using CRISPR/Cpf1. Homozygous Slc17a5R39C/R39C mice recapitulated key features of FSASD, including biochemical accumulation of free sialic acid, ataxia, tremors, seizures and shortened lifespan. Neuropathological analyses revealed widespread CNS hypomyelination, with relatively preserved peripheral nervous system myelination, while transcriptomic profiling showed broad suppression of myelin-associated genes and a cerebellum-specific inflammatory signature. This was accompanied by pronounced astrogliosis, progressive Purkinje cell degeneration and elevated neurofilament proteins, including serum neurofilament light polypeptide. Altogether, the Slc17a5R39C/R39C model of FSASD provides critical insights into disease pathogenesis, highlights region-specific neurodegenerative vulnerabilities, and establishes a robust preclinical platform for mechanistic investigation and therapeutic development.

Indexed as

Demyelinating DiseasesNerve DegenerationPurkinje CellsSialic Acid Storage DiseaseAnimalsDisease Models, AnimalMyelin SheathN-Acetylneuraminic AcidOrganic Anion TransportersSymportersN-Acetylneuraminic AcidOrganic Anion Transporterssialic acid transport proteinsSymportersMyelin developmentPurkinje cell lossRare disordersSialic acidSialin

Identifiers

PMID42187043
PMCPMC13474576

What OpenQuestion holds

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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.