Phenotyping GABA transaminase deficiency: a case description and literature review
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.4/2050 |
Resumo: | Gamma-aminobutyric acid transaminase (GABA-T) deficiency is an autosomal recessive disorder reported in only three unrelated families. It is caused by mutations in the ABAT gene, which encodes 4-aminobutyrate transaminase, an enzyme of GABA catabolism and mitochondrial nucleoside salvage. We report the case of a boy, deceased at 12 months of age, with early-onset epileptic encephalopathy, severe psychomotor retardation, hypotonia, lower-limb hyporeflexia, central hypoventilation, and rapid increase in weight and, to a lesser rate, length and head circumference. He presented signs of premature pubarche, thermal instability, and water-electrolyte imbalance. Serum total testosterone was elevated (43.3 ng/dl; normal range <16), as well as serum growth hormone (7.7 ng/ml; normal range <1). Brain magnetic resonance imaging (MRI) showed decreased myelination and generalized brain atrophy, later confirmed by post-mortem examination. ABAT gene sequencing was performed post-mortem, identifying a homozygous variant c.888G > T (p.Gln296His),not previously described. In vitro analysis concluded that this variant is pathogenic. The clinical features of this patient are similar to those reported so far in GABA-T deficiency. However, distinct mutations may have a different effect on enzymatic activity, which potentially could lead to a variable clinical outcome. Clinical investigation aiming for a diagnosis should not end with the patient's death, as it may allow a more precise genetic counselling for the family. |
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Phenotyping GABA transaminase deficiency: a case description and literature reviewErros Inatos do Metabolismo4-Aminobutirato Transaminase/deficiência4-Aminobutirato Transaminase/genéticaGamma-aminobutyric acid transaminase (GABA-T) deficiency is an autosomal recessive disorder reported in only three unrelated families. It is caused by mutations in the ABAT gene, which encodes 4-aminobutyrate transaminase, an enzyme of GABA catabolism and mitochondrial nucleoside salvage. We report the case of a boy, deceased at 12 months of age, with early-onset epileptic encephalopathy, severe psychomotor retardation, hypotonia, lower-limb hyporeflexia, central hypoventilation, and rapid increase in weight and, to a lesser rate, length and head circumference. He presented signs of premature pubarche, thermal instability, and water-electrolyte imbalance. Serum total testosterone was elevated (43.3 ng/dl; normal range <16), as well as serum growth hormone (7.7 ng/ml; normal range <1). Brain magnetic resonance imaging (MRI) showed decreased myelination and generalized brain atrophy, later confirmed by post-mortem examination. ABAT gene sequencing was performed post-mortem, identifying a homozygous variant c.888G > T (p.Gln296His),not previously described. In vitro analysis concluded that this variant is pathogenic. The clinical features of this patient are similar to those reported so far in GABA-T deficiency. However, distinct mutations may have a different effect on enzymatic activity, which potentially could lead to a variable clinical outcome. Clinical investigation aiming for a diagnosis should not end with the patient's death, as it may allow a more precise genetic counselling for the family.RIHUCLouro, PRamos, LRobalo, CCancelinha, CDinis, AVeiga, RPina, RRebelo, OPop, ADiogo, LSalomons, GSGarcia, P2017-07-17T14:06:30Z2016-092016-09-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.4/2050engJ Inherit Metab Dis. 2016 Sep;39(5):743-7.10.1007/s10545-016-9951-zinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-11T14:23:21Zoai:rihuc.huc.min-saude.pt:10400.4/2050Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:04:31.319455Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Phenotyping GABA transaminase deficiency: a case description and literature review |
title |
Phenotyping GABA transaminase deficiency: a case description and literature review |
spellingShingle |
Phenotyping GABA transaminase deficiency: a case description and literature review Louro, P Erros Inatos do Metabolismo 4-Aminobutirato Transaminase/deficiência 4-Aminobutirato Transaminase/genética |
title_short |
Phenotyping GABA transaminase deficiency: a case description and literature review |
title_full |
Phenotyping GABA transaminase deficiency: a case description and literature review |
title_fullStr |
Phenotyping GABA transaminase deficiency: a case description and literature review |
title_full_unstemmed |
Phenotyping GABA transaminase deficiency: a case description and literature review |
title_sort |
Phenotyping GABA transaminase deficiency: a case description and literature review |
author |
Louro, P |
author_facet |
Louro, P Ramos, L Robalo, C Cancelinha, C Dinis, A Veiga, R Pina, R Rebelo, O Pop, A Diogo, L Salomons, GS Garcia, P |
author_role |
author |
author2 |
Ramos, L Robalo, C Cancelinha, C Dinis, A Veiga, R Pina, R Rebelo, O Pop, A Diogo, L Salomons, GS Garcia, P |
author2_role |
author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
RIHUC |
dc.contributor.author.fl_str_mv |
Louro, P Ramos, L Robalo, C Cancelinha, C Dinis, A Veiga, R Pina, R Rebelo, O Pop, A Diogo, L Salomons, GS Garcia, P |
dc.subject.por.fl_str_mv |
Erros Inatos do Metabolismo 4-Aminobutirato Transaminase/deficiência 4-Aminobutirato Transaminase/genética |
topic |
Erros Inatos do Metabolismo 4-Aminobutirato Transaminase/deficiência 4-Aminobutirato Transaminase/genética |
description |
Gamma-aminobutyric acid transaminase (GABA-T) deficiency is an autosomal recessive disorder reported in only three unrelated families. It is caused by mutations in the ABAT gene, which encodes 4-aminobutyrate transaminase, an enzyme of GABA catabolism and mitochondrial nucleoside salvage. We report the case of a boy, deceased at 12 months of age, with early-onset epileptic encephalopathy, severe psychomotor retardation, hypotonia, lower-limb hyporeflexia, central hypoventilation, and rapid increase in weight and, to a lesser rate, length and head circumference. He presented signs of premature pubarche, thermal instability, and water-electrolyte imbalance. Serum total testosterone was elevated (43.3 ng/dl; normal range <16), as well as serum growth hormone (7.7 ng/ml; normal range <1). Brain magnetic resonance imaging (MRI) showed decreased myelination and generalized brain atrophy, later confirmed by post-mortem examination. ABAT gene sequencing was performed post-mortem, identifying a homozygous variant c.888G > T (p.Gln296His),not previously described. In vitro analysis concluded that this variant is pathogenic. The clinical features of this patient are similar to those reported so far in GABA-T deficiency. However, distinct mutations may have a different effect on enzymatic activity, which potentially could lead to a variable clinical outcome. Clinical investigation aiming for a diagnosis should not end with the patient's death, as it may allow a more precise genetic counselling for the family. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-09 2016-09-01T00:00:00Z 2017-07-17T14:06:30Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.4/2050 |
url |
http://hdl.handle.net/10400.4/2050 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
J Inherit Metab Dis. 2016 Sep;39(5):743-7. 10.1007/s10545-016-9951-z |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799131707800027136 |