Evidence map›Paper›PMID 30829465›Full record

ArticleMolecular genetics & genomic medicine2019

Rett syndrome (MECP2) and succinic semialdehyde dehydrogenase (ALDH5A1) deficiency in a developmentally delayed female.

Madalyn Brown, Paula Ashcraft, Erland Arning, Teodoro Bottiglieri, William McClintock, Frank Giancola, David Lieberman, Natalie S Hauser, Rebecca Miller, Jean-Baptiste Roullet and 2 more

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In one paragraph

Article in Molecular genetics & genomic medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.2field-weighted citation impact, top 39% 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

2 citing papers in PubMed, 1 citations in OpenAlex.

  1. Article
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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

12 authors at 6 institutions in 1 country.

Madalyn BrownDepartment of Pharmacotherapy, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, Washington.
Paula AshcraftBaylor Scott & White Research Institute, Institute of Metabolic Disease, Dallas, Texas.
Erland ArningBaylor Scott & White Research Institute, Institute of Metabolic Disease, Dallas, Texas.
Teodoro BottiglieriBaylor Scott & White Research Institute, Institute of Metabolic Disease, Dallas, Texas.
William McClintockPediatric Specialists of Virginia, Fairfax, Virginia.
Frank GiancolaPediatric Care of Northern Virginia, Manassas, Virginia.
David LiebermanDepartment of Neurology, Boston Children's Hospital, Harvard School of Medicine, Boston, Massachusetts.
Natalie S HauserFulgent Genetics, Temple City, California.
Rebecca MillerFulgent Genetics, Temple City, California.
Jean-Baptiste RoulletDepartment of Pharmacotherapy, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, Washington.
Phillip PearlDepartment of Neurology, Boston Children's Hospital, Harvard School of Medicine, Boston, Massachusetts.
K Michael GibsonDepartment of Pharmacotherapy, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, Washington.
Research Institute of Dallas · USWashington State University Spokane · USBoston Children's Hospital · USTemple College · USUniversity of Northern Virginia · USVirginia Cancer Specialists · US

Funding

Research_ProjectU54HD090257 · NICHD · CHILDREN'S RESEARCH INSTITUTE · PI VITTORIO GALLO, VITTORIO GALLO VITTORIO GALLO · 2016 to 2020
$5.9M
NICHD NIH HHS U54 HD090257
6 · The paper itself

Abstract

backgroundWe present a patient with Rett syndrome (RTT; MECP2) and autosomal-recessive succinic semialdehyde dehydrogenase deficiency (SSADHD; ALDH5A1 (aldehyde dehydrogenase 5a1 = SSADH), in whom the current phenotype exhibits features of SSADHD (hypotonia, global developmental delay) and RTT (hand stereotypies, gait anomalies).

methodsγ-Hydroxybutyric acid (GHB) was quantified by UPLC-tandem mass spectrometry, while mutation analysis followed standard methodology of whole-exome sequencing.

resultsThe biochemical hallmark of SSADHD, GHB was increased in the proband's dried bloodspot (DBS; 673 µM; previous SSADHD DBSs (n = 7), range 124-4851 µM); control range (n = 2,831), 0-78 µM. The proband was compound heterozygous for pathogenic ALDH5A1 mutations (p.(Asn418IlefsTer39); maternal; p.(Gly409Asp); paternal) and a de novo RTT nonsense mutation in MECP2 (p.Arg255*).

conclusionThe major inhibitory neurotransmitter, γ-aminobutyric acid (GABA), is increased in SSADHD but normal in RTT, although there are likely regional changes in GABA receptor distribution. GABAergic anomalies occur in both disorders, each featuring an autism spectrum phenotype. What effect the SSADHD biochemical anomalies (elevated GABA, GHB) might play in the neurodevelopmental/epileptic phenotype of our patient is currently unknown.

Indexed as

PhenotypeAmino Acid Metabolism, Inborn ErrorsChild, PreschoolDevelopmental DisabilitiesFemaleHumansMethyl-CpG-Binding Protein 2Rett SyndromeSuccinate-Semialdehyde DehydrogenaseALDH5A1 protein, humanMECP2 protein, humanMethyl-CpG-Binding Protein 2Succinate-Semialdehyde Dehydrogenaseautism spectrum disorderGABA (γ-aminobutyric acid)GHB (γ-hydroxybutyric acid)Rett syndromesuccinic semialdehyde dehydrogenasesuccinic semialdehyde dehydrogenase deficiency

Identifiers

PMID30829465
PMCPMC6503008
OpenAlexW2918266158

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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.