{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:01:52Z","timestamp":1753869712498,"version":"3.41.2"},"reference-count":24,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,3,4]],"date-time":"2019-03-04T00:00:00Z","timestamp":1551657600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>We present a patient with Rett syndrome (RTT; <jats:italic>MECP2<\/jats:italic>) and autosomal\u2010recessive succinic semialdehyde dehydrogenase deficiency (SSADHD; <jats:italic>ALDH5A1<\/jats:italic> (aldehyde dehydrogenase 5a1\u00a0=\u00a0SSADH), in whom the current phenotype exhibits features of SSADHD (hypotonia, global developmental delay) and RTT (hand stereotypies, gait anomalies).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>\u03b3\u2010Hydroxybutyric acid (GHB) was quantified by UPLC\u2010tandem mass spectrometry, while mutation analysis followed standard methodology of whole\u2010exome sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The biochemical hallmark of SSADHD, GHB was increased in the proband's dried bloodspot (DBS; 673\u00a0\u00b5M; previous SSADHD DBSs (<jats:italic>n<\/jats:italic>\u00a0=\u00a07), range 124\u20134851\u00a0\u00b5M); control range (<jats:italic>n<\/jats:italic>\u00a0=\u00a02,831), 0\u201378\u00a0\u00b5M. The proband was compound heterozygous for pathogenic <jats:italic>ALDH5A1<\/jats:italic> mutations (p.(Asn418IlefsTer39); maternal; p.(Gly409Asp); paternal) and a de novo RTT nonsense mutation in <jats:italic>MECP2<\/jats:italic> (p.Arg255*).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The major inhibitory neurotransmitter, \u03b3\u2010aminobutyric 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.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.629","type":"journal-article","created":{"date-parts":[[2019,3,4]],"date-time":"2019-03-04T10:14:37Z","timestamp":1551694477000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Rett syndrome (<i>MECP2<\/i>) and succinic semialdehyde dehydrogenase (<i>ALDH5A1<\/i>) deficiency in a developmentally delayed female"],"prefix":"10.1002","volume":"7","author":[{"given":"Madalyn","family":"Brown","sequence":"first","affiliation":[{"name":"Department of Pharmacotherapy, College of Pharmacy and Pharmaceutical Sciences Washington State University Spokane Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula","family":"Ashcraft","sequence":"additional","affiliation":[{"name":"Baylor Scott &amp; White Research Institute Institute of Metabolic Disease Dallas Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erland","family":"Arning","sequence":"additional","affiliation":[{"name":"Baylor Scott &amp; White Research Institute Institute of Metabolic Disease Dallas Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teodoro","family":"Bottiglieri","sequence":"additional","affiliation":[{"name":"Baylor Scott &amp; White Research Institute Institute of Metabolic Disease Dallas Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"McClintock","sequence":"additional","affiliation":[{"name":"Pediatric Specialists of Virginia Fairfax Virginia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Giancola","sequence":"additional","affiliation":[{"name":"Pediatric Care of Northern Virginia Manassas Virginia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Lieberman","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston Children\u2019s Hospital Harvard School of Medicine Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie S.","family":"Hauser","sequence":"additional","affiliation":[{"name":"Fulgent Genetics Temple City California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Miller","sequence":"additional","affiliation":[{"name":"Fulgent Genetics Temple City California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean\u2010Baptiste","family":"Roullet","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy, College of Pharmacy and Pharmaceutical Sciences Washington State University Spokane Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phillip","family":"Pearl","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston Children\u2019s Hospital Harvard School of Medicine Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. 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