Evidence map›Paper›PMID 39919676›Full record

ArticleMolecular genetics and metabolism2025

The neuropsychological profile of SSADH deficiency, a neurotransmitter disorder of GABA metabolism.

Itay Tokatly Latzer, Ellen Hanson, Mariarita Bertoldi, Melissa L DiBacco, Deniz Aygun, Onur Afacan, Àngeles García-Cazorla, Natalia Juliá-Palacios, Thomas Opladen, Oya Kuseyri Hübschmann and 7 more

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Article in Molecular genetics and metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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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

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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. Review
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

17 authors.

Itay Tokatly LatzerDepartment of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; School of Medicine, Faculty of Medical and Health Sciences, Tel-Aviv University, Tel Aviv, Israel. Electronic address: itay.tokatlylatzer@childrens.harvard.edu.
Ellen HansonHuman Neurobehavioral Core Services, Division of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Rosamund Stone Zander Translational Neuroscience Center, Boston Children's Hospital, MA 02115, USA. Electronic address: Ellen.Hanson@childrens.harvard.edu.
Mariarita BertoldiDepartment of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona, Italy. Electronic address: mita.bertoldi@univr.it.
Melissa L DiBaccoDepartment of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: Melissa.DiBacco@childrens.harvard.edu.
Deniz AygunDepartment of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: deniz.aygun@einsteinmed.edu.
Onur AfacanDepartment of Radiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: onur.afacan@childrens.harvard.edu.
Àngeles García-CazorlaNeurometabolic Unit, Neurology Department, Institut de Recerca, Hospital Sant Joan de Déu, Barcelona, Spain. Electronic address: agarcia@sjdhospitalbarcelona.org.
Natalia Juliá-PalaciosNeurometabolic Unit, Neurology Department, Institut de Recerca, Hospital Sant Joan de Déu, Barcelona, Spain. Electronic address: nataliaalexandra.julia@sjd.es.
Thomas OpladenHeidelberg University, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Department I, Division of Pediatric Neurology and Metabolic Medicine, Heidelberg, Germany. Electronic address: Thomas.Opladen@med.uni-heidelberg.de.
Oya Kuseyri HübschmannHeidelberg University, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Department I, Division of Pediatric Neurology and Metabolic Medicine, Heidelberg, Germany. Electronic address: Oya.KuseyriHuebschmann@med.uni-heidelberg.de.
Kathrin JeltschHeidelberg University, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Department I, Division of Pediatric Neurology and Metabolic Medicine, Heidelberg, Germany. Electronic address: Kathrin.Jeltsch@med.uni-heidelberg.de.
Petra AdenDepartment of Clinical Neurosciences for Children, Oslo University Hospital, Oslo, Norway. Electronic address: UXPEAD@ous-hf.no.
Mari OppebøenDepartment of Clinical Neurosciences for Children, Oslo University Hospital, Oslo, Norway. Electronic address: maropp@ous-hf.no.
Alexander RotenbergDepartment of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA 02115, USA. Electronic address: alexander.rotenberg@childrens.harvard.edu.
Melissa TsuboyamaDepartment of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: melissa.tsuboyama@childrens.harvard.edu.
Jean-Baptiste RoulletDepartment of Pharmacotherapy, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA, USA. Electronic address: j.roullet@wsu.edu.
Phillip L PearlDepartment of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: Phillip.Pearl@childrens.harvard.edu.

Funding

Genetic Analysis and Manipulation Core (GAEC)P50HD105351 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI Hisashi Umemori · 2021 to 2026
$9.4M
Natural History of Succinic Semialdehyde Dehydrogenase Deficiency (SSADHD), a Heritable Disorder of GABA MetabolismR01HD091142 · NICHD · WASHINGTON STATE UNIVERSITY · PI Phillip Lawrence Pearl · 2018 to 2026
$5.3M
Developing an inducible mouse model for gene replacement therapy in Succinic Semialdehyde Dehydrogenase Deficiency (SSADHD)R21NS121858 · NINDS · BOSTON CHILDREN'S HOSPITAL · PI ROTENBERG, ALEXANDER · 2022 to 2023
$487k
NICHD NIH HHS P50 HD105351NICHD NIH HHS R01 HD091142NINDS NIH HHS R21 NS121858
6 · The paper itself

Abstract

BACKGROUND AND

objectivesSuccinic semialdehyde dehydrogenase deficiency (SSADHD) is an inherited metabolic disorder resulting in hyper-physiologic concentrations of the neurotransmitter γ-aminobutyrate (GABA). This study aims to provide the most comprehensive description, to date, of the neuropsychological profile of individuals with SSADHD and assess whether neuroimaging, neurophysiologic, and biochemical indices of cortical inhibition correlate with those of standardized behavioral tests.

methodsParticipants enrolled in the SSADHD Natural History Study underwent medical and neurological examinations, magnetic resonance imaging (MRI) and spectroscopy (MRS), biochemical tests of GABA and its related metabolites, transcranial magnetic stimulation (TMS), and gene expression quantification, as well as complete neuropsychological assessment including standardized measures for cognition, adaptive skills, motor function, receptive and expressive language, autism spectrum disorder, and behavior problems.

resultsThe neuropsychological profile of the study's 65 enrollees [54 % females, median (interquartile range) age 9.6 (5.4-14.7)] consisted almost universally of intellectual disability, delays in adaptive skills, and deficits in expressive more than receptive language. Autism Spectrum Disorder was noted in ∼50 %, and behavioral problems in ∼70 %, predominated by obsessive-compulsive behaviors and attention problems but also including affective problems, anxiety, and, rarely, aggression and possible psychosis. Correlation analyses showed that increased internalizing, externalizing, and overall psychiatric morbidity significantly correlated with increasing age (R = 0.391, p = 0.033), as well as age-independent indices representing decreased cortical inhibition such as lower MRS-derived GABA (R = -0.530, p = 0.029) and TMS-derived resting motor threshold (R = -0.418, p = 0.053). DISCUSSION: The natural history study of SSADHD indicates that intellectual disability, delayed adaptive skills, and expressive>receptive language deficits are nearly universal, with behavior problems in the vast majority. Increased psychiatric morbidity in SSADHD with age-independent decreased cortical inhibition may serve as the basis for establishing disorder-specific biomarkers for behavioral and psychiatric outcomes in SSADHD and other non-syndromic psychiatric disorders.

Indexed as

Amino Acid Metabolism, Inborn Errorsgamma-Aminobutyric AcidSuccinate-Semialdehyde DehydrogenaseAdolescentAutism Spectrum DisorderChildChild, PreschoolDevelopmental DisabilitiesFemaleHumansIntellectual DisabilityMagnetic Resonance ImagingMaleNeuropsychological TestsNeurotransmitter Agentsgamma-Aminobutyric AcidNeurotransmitter AgentsSuccinate-Semialdehyde DehydrogenaseBehaviorDevelopmentalGamma-aminobutyric acidPsychiatricSuccinic semialdehyde dehydrogenase

Identifiers

PMID39919676
PMCPMC11879317

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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.