OMIMOnlineMendelianInheritanceinManAll DatabasesPubMedNucleotideProteinGenomeStructurePMCTaxonomyOMIM SearchPubMedProteinNucleotideCoreNucleotideGSSESTStructureGenomeBooksCancerChromosomesConservedDomainsdbGaP3DDomainsGeneGenomeProjectGENSATGEOProfilesGEODataSetsHomoloGeneJournalsMeSHNCBIWebSiteNLMCatalogOMIAOMIMPMCPopSetProbeProteinClustersPubChemBioAssayPubChemCompoundPubChemSubstanceSNPTaxonomyToolKitUniGeneUniSTSLimitsPreview/IndexHistoryClipboardDetailsDisplayTitlesDetailedClinicalSynopsisAllelicVariantsASN1XMLLinkOutRelatedEntriesBookLinksGeneLinksGenomeLinksGEOProfileLinksHomoloGeneLinksNucleotideLinksOMIALinksPubChemBioAssayLinksPMCLinksProteinLinksPubMed(calculated)LinksPubMed(cited)LinksSNPLinksGeneGenotypeLinksStructureLinksUniGeneLinksUniSTSLinksShow5102050100200500SendtoTextFilePrinterClipboardAll1OMIMdbSNP0OMIMUniSTS0+137150GeneTestsLinks4@AMINOBUTYRATEAMINOTRANSFERASEABATAlternativetitlessymbolsGAMMAAMINOBUTYRATETRANSAMINASEGABATGABATRANSFERASEGABATRANSAMINASEDEFICIENCYINCLUDEDGenemaplocus16p133TEXTGammaaminobutyratetransaminase(EC26119)isresponsibleforcatabolismofgammaaminobutyricacid(GABA)animportantmostlyinhibitoryneurotransmitterinthecentralnervoussystemintosuccinicsemialdehydeTheactiveenzymeisahomodimerof50kDsubunitscomplexedtopyridoxal5phosphateGABATispresentinseveraltissuesinadditiontobrainandismostactiveinliverOseiandChurchich(1995)usedaprobefromthepigGABATcDNAtoscreenahumanbraincDNAlibraryTheyidentifiedahumanGABATcDNAwhichencodesa500aminoacidproteinthatisover95%similartothepigproteinGABAisestimatedtobepresentinnearlyonethirdofhumansynapsesAdefectinthedegradationofGABA(succinicsemialdehydedehydrogenasedeficiency)resultsinasyndromeofmentalretardationhypotoniaandataxia(271980)AnotherhereditarydefectofGABAcatabolismultimatelyassociatedwithGABATwasdiscoveredbyJaekenetal(1984)inthestudyof2sibsofconsanguineousFlemishparentswhopresentedwithseverebraindisorderleukodystrophyandacceleratedgrowthThepropositahadseverepsychomotorretardationhypotoniaandhyperreflexiaHerlengthwhichatbirthwasatthe3rdpercentilerosetothe99thpercentilebyage24monthsCSFshowedhighlevelsoffreeGABAhomocarnosine(adipeptideofGABAandhistidine)andbetaalanine(analternativesubstrateforGABAtransaminase)LiverGABAtransaminasewasdeficientFastingplasmagrowthhormonelevelswereincreasedBrainevokedresponsesweresuggestiveofleukodystrophyAbrotherwhoshowedasimilarclinicalpicturehaddiedat1yearofagePostmortemshowedleukodystrophyofthetypeseeninaminoacidopathiessuchasphenylketonuriaThepropositadiedatage25months(Gibsonetal1986)Gibsonetal(1985)establishedautosomalrecessiveinheritancebyfindingevidenceofheterozygosityinbothparentsandahealthysibandhomozygosityforGABAtransferasedeficiencyintheaffectedFlemishchildJeremiahandPovey(1981)suggestedthatGABATinliverandbrainiscontrolledby2codominantalleleswithafrequencyinaCaucasianpopulationof056and044A3bandedpatterninheterozygotessuggestedthatGABATisadimericproteinBhattacharyyaetal(1985)gavegenefrequenciesforChineseIndiansandMalayslivinginSingaporeanddescribedanewalleleMedinaKauweetal(1999)describedasecondpatientwithGABATdeficiencyThephenotypeinbothincludedpsychomotorretardationhypotoniahyperreflexialethargyrefractoryseizuresandEEGabnormalitiesThesecondpatientdidnothaveincreasedlineargrowthasafeatureofthedisorderTheInternationalRadiationHybridMappingConsortiummappedtheABATgeneto16p133(RH69040)DataongenefrequenciesofallelicvariantsweretabulatedbyRoychoudhuryandNei(1988)(selectedexamples)0001GABATRANSAMINASEDEFICIENCY[ABATARG220LYS]IntheoriginalcasedescribedbyJaekenetal(1984)MedinaKauweetal(1999)identifiedanAtoGtransitionatnucleotide754oftheABATgeneinlymphoblastcDNAThismutationresultedinsubstitutionofaninvariantarginineataminoacid220bylysineExpressionofthemutantinEcolifollowedbyisolationandenzymaticcharacterizationoftherecombinantproteinrevealedanenzymewhoseVmaxwasreducedto25%ofwildtypeactivityThesecondalleleinthepatientremainedunidentified0002GABATRANSAMINASEDEFICIENCY[ABAT3PRIMEDELETION]InapatientwithGABAtransaminasedeficiencyMedinaKauweetal(1999)identifiedadeletionofthe3primeendoftheGABATgeneREFERENCES1BhattacharyyaSPSahaNWeeKPGammaaminobutyricacidtransaminase(GABAT)polymorphismamongethnicgroupsinSingaporewithreportofanewalleleAmJHumGenet373583611985PubMedID39850102GibsonKMNyhanWLJaekenJInbornerrorsofGABAmetabolismBioEssays424271986PubMedID37901083GibsonKMSweetmanLNyhanWLJansenIJaekenJDemonstrationof4aminobutyricacidaminotransferasedeficiencyinlymphocytesandlymphoblastsJInheritMetabDis82042081985PubMedID39395444JaekenJCasaerPdeCockPCorbeelLEeckelsREggermontESchechterPJBrucherJMGammaaminobutyricacidtransaminasedeficiencyanewlyrecognizedinbornerrorofneurotransmittermetabolismNeuropediatrics151651691984PubMedID61487085JaekenJCasaerPDeCockPetalGammaaminobutyricacidtransaminasedeficiencyanewlyrecognizedinbornerrorofneurotransmittermetabolismNeuropediatrics151651691984PubMedID61487086JeremiahSPoveySThebiochemicalgeneticsofhumangammaaminobutyricacidtransaminaseAnnHumGenet452312361981PubMedID73052807MedinaKauweLKTobinAJDeMeirleirLJaekenJJakobsCNyhanWLGibsonKM4aminobutyrateaminotransferase(GABAtransaminase)deficiencyJInheritMetabDis224144271999PubMedID104077788OseiYDChurchichJEScreeningandsequencedeterminationofacDNAencodingthehumanbrain4aminobutyrateaminotransferaseGene1551851871995PubMedID77210889RoychoudhuryAKNeiMHumanPolymorphicGenesWorldDistributionNewYorkOxfordUnivPress(pub)1988CONTRIBUTORSAdaHamoshupdated7/15/1999AlanFScottupdated6/21/1995CREATIONDATEVictorAMcKusick6/4/1986EDITHISTORYmgross3/17/2004carol10/25/2000joanna2/23/2000alopez7/26/1999terry7/15/1999alopez8/20/1998joanna5/7/1998joanna5/7/1998mimadm9/24/1994warfield2/17/1994supermim3/16/1992carol2/12/1991carol2/4/1991Copyright©19662007JohnsHopkinsUniversityDisplayTitlesDetailedClinicalSynopsisAllelicVariantsASN1XMLLinkOutRelatedEntriesBookLinksGeneLinksGenomeLinksGEOProfileLinksHomoloGeneLinksNucleotideLinksOMIALinksPubChemBioAssayLinksPMCLinksProteinLinksPubMed(calculated)LinksPubMed(cited)LinksSNPLinksGeneGenotypeLinksStructureLinksUniGeneLinksUniSTSLinksShow5102050100200500SendtoTextFilePrinterClipboardDisclaimerWritetotheHelpDeskPrivacyPolicyNCBINLMNIH