A Multinational Study of Acute and Long‐Term Outcomes of Type 1 Galactosemia Patients Who Carry the S135L (c.404C > T) Variant of GALT

Detalhes bibliográficos
Autor(a) principal: Katler, Q
Data de Publicação: 2022
Outros Autores: Stepien, K, Paull, N, Patel, S, Adams, M, Balci, M, Berry, G, Bosch, A, DeLaO, A, Demirbas, D, Edman, J, Ficicioglu, C, Goff, M, Hacker, S, Knerr, I, Lancaster, K, Li, H, Mendelsohn, B, Nichols, B, Rezende Pinto, W, César Rocha, J, Rubio‐Gozalbo, ME, Saad‐Naguib, M, Scholl‐Buergi, S, Searcy, S, Souza, P, Wittenauer, A, Fridovich‐Keil, J
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.17/4715
Resumo: Patients with galactosemia who carry the S135L (c.404C > T) variant of galactose-1-P uridylyltransferase (GALT), documented to encode low-level residual GALT activity, have been under-represented in most prior studies of outcomes in Type 1 galactosemia. What is known about the acute and long-term outcomes of these patients, therefore, is based on very limited data. Here, we present a study comparing acute and long-term outcomes of 12 patients homozygous for S135L, 25 patients compound heterozygous for S135L, and 105 patients homozygous for two GALT-null (G) alleles. This is the largest cohort of S135L patients characterized to date. Acute disease following milk exposure in the newborn period was common among patients in all 3 comparison groups in our study, as were long-term complications in the domains of speech, cognition, and motor outcomes. In contrast, while at least 80% of both GALT-null and S135L compound heterozygous girls and women showed evidence of an adverse ovarian outcome, prevalence was only 25% among S135L homozygotes. Further, all young women in this study with even one copy of S135L achieved spontaneous menarche; this is true for only about 33% of women with classic galactosemia. Overall, we observed that while most long-term outcomes trended milder among groups of patients with even one copy of S135L, many individual patients, either homozygous or compound heterozygous for S135L, nonetheless experienced long-term outcomes that were not mild. This was true despite detection by newborn screening and both early and life-long dietary restriction of galactose. This information should empower more evidence-based counseling for galactosemia patients with S135L.
id RCAP_a021984ff1ca27061b646fa8ae72875e
oai_identifier_str oai:repositorio.chlc.min-saude.pt:10400.17/4715
network_acronym_str RCAP
network_name_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository_id_str 7160
spelling A Multinational Study of Acute and Long‐Term Outcomes of Type 1 Galactosemia Patients Who Carry the S135L (c.404C > T) Variant of GALTHCC ENDHumansFemaleAllelesGalactoseGalactosemias* / diagnosisGalactosemias* / geneticsHomozygoteInfant, NewbornUTP-Hexose-1-Phosphate Uridylyltransferase / geneticsPatients with galactosemia who carry the S135L (c.404C > T) variant of galactose-1-P uridylyltransferase (GALT), documented to encode low-level residual GALT activity, have been under-represented in most prior studies of outcomes in Type 1 galactosemia. What is known about the acute and long-term outcomes of these patients, therefore, is based on very limited data. Here, we present a study comparing acute and long-term outcomes of 12 patients homozygous for S135L, 25 patients compound heterozygous for S135L, and 105 patients homozygous for two GALT-null (G) alleles. This is the largest cohort of S135L patients characterized to date. Acute disease following milk exposure in the newborn period was common among patients in all 3 comparison groups in our study, as were long-term complications in the domains of speech, cognition, and motor outcomes. In contrast, while at least 80% of both GALT-null and S135L compound heterozygous girls and women showed evidence of an adverse ovarian outcome, prevalence was only 25% among S135L homozygotes. Further, all young women in this study with even one copy of S135L achieved spontaneous menarche; this is true for only about 33% of women with classic galactosemia. Overall, we observed that while most long-term outcomes trended milder among groups of patients with even one copy of S135L, many individual patients, either homozygous or compound heterozygous for S135L, nonetheless experienced long-term outcomes that were not mild. This was true despite detection by newborn screening and both early and life-long dietary restriction of galactose. This information should empower more evidence-based counseling for galactosemia patients with S135L.WileyRepositório do Centro Hospitalar Universitário de Lisboa Central, EPEKatler, QStepien, KPaull, NPatel, SAdams, MBalci, MBerry, GBosch, ADeLaO, ADemirbas, DEdman, JFicicioglu, CGoff, MHacker, SKnerr, ILancaster, KLi, HMendelsohn, BNichols, BRezende Pinto, WCésar Rocha, JRubio‐Gozalbo, MESaad‐Naguib, MScholl‐Buergi, SSearcy, SSouza, PWittenauer, AFridovich‐Keil, J2023-10-09T14:32:54Z2022-112022-11-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.17/4715engJ Inherit Metab Dis . 2022 Nov;45(6):1106-1117.10.1002/jimd.12556info: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:RCAAP2023-10-15T06:33:07Zoai:repositorio.chlc.min-saude.pt:10400.17/4715Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:35:47.109076Repositório 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 A Multinational Study of Acute and Long‐Term Outcomes of Type 1 Galactosemia Patients Who Carry the S135L (c.404C > T) Variant of GALT
title A Multinational Study of Acute and Long‐Term Outcomes of Type 1 Galactosemia Patients Who Carry the S135L (c.404C > T) Variant of GALT
spellingShingle A Multinational Study of Acute and Long‐Term Outcomes of Type 1 Galactosemia Patients Who Carry the S135L (c.404C > T) Variant of GALT
Katler, Q
HCC END
Humans
Female
Alleles
Galactose
Galactosemias* / diagnosis
Galactosemias* / genetics
Homozygote
Infant, Newborn
UTP-Hexose-1-Phosphate Uridylyltransferase / genetics
title_short A Multinational Study of Acute and Long‐Term Outcomes of Type 1 Galactosemia Patients Who Carry the S135L (c.404C > T) Variant of GALT
title_full A Multinational Study of Acute and Long‐Term Outcomes of Type 1 Galactosemia Patients Who Carry the S135L (c.404C > T) Variant of GALT
title_fullStr A Multinational Study of Acute and Long‐Term Outcomes of Type 1 Galactosemia Patients Who Carry the S135L (c.404C > T) Variant of GALT
title_full_unstemmed A Multinational Study of Acute and Long‐Term Outcomes of Type 1 Galactosemia Patients Who Carry the S135L (c.404C > T) Variant of GALT
title_sort A Multinational Study of Acute and Long‐Term Outcomes of Type 1 Galactosemia Patients Who Carry the S135L (c.404C > T) Variant of GALT
author Katler, Q
author_facet Katler, Q
Stepien, K
Paull, N
Patel, S
Adams, M
Balci, M
Berry, G
Bosch, A
DeLaO, A
Demirbas, D
Edman, J
Ficicioglu, C
Goff, M
Hacker, S
Knerr, I
Lancaster, K
Li, H
Mendelsohn, B
Nichols, B
Rezende Pinto, W
César Rocha, J
Rubio‐Gozalbo, ME
Saad‐Naguib, M
Scholl‐Buergi, S
Searcy, S
Souza, P
Wittenauer, A
Fridovich‐Keil, J
author_role author
author2 Stepien, K
Paull, N
Patel, S
Adams, M
Balci, M
Berry, G
Bosch, A
DeLaO, A
Demirbas, D
Edman, J
Ficicioglu, C
Goff, M
Hacker, S
Knerr, I
Lancaster, K
Li, H
Mendelsohn, B
Nichols, B
Rezende Pinto, W
César Rocha, J
Rubio‐Gozalbo, ME
Saad‐Naguib, M
Scholl‐Buergi, S
Searcy, S
Souza, P
Wittenauer, A
Fridovich‐Keil, J
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório do Centro Hospitalar Universitário de Lisboa Central, EPE
dc.contributor.author.fl_str_mv Katler, Q
Stepien, K
Paull, N
Patel, S
Adams, M
Balci, M
Berry, G
Bosch, A
DeLaO, A
Demirbas, D
Edman, J
Ficicioglu, C
Goff, M
Hacker, S
Knerr, I
Lancaster, K
Li, H
Mendelsohn, B
Nichols, B
Rezende Pinto, W
César Rocha, J
Rubio‐Gozalbo, ME
Saad‐Naguib, M
Scholl‐Buergi, S
Searcy, S
Souza, P
Wittenauer, A
Fridovich‐Keil, J
dc.subject.por.fl_str_mv HCC END
Humans
Female
Alleles
Galactose
Galactosemias* / diagnosis
Galactosemias* / genetics
Homozygote
Infant, Newborn
UTP-Hexose-1-Phosphate Uridylyltransferase / genetics
topic HCC END
Humans
Female
Alleles
Galactose
Galactosemias* / diagnosis
Galactosemias* / genetics
Homozygote
Infant, Newborn
UTP-Hexose-1-Phosphate Uridylyltransferase / genetics
description Patients with galactosemia who carry the S135L (c.404C > T) variant of galactose-1-P uridylyltransferase (GALT), documented to encode low-level residual GALT activity, have been under-represented in most prior studies of outcomes in Type 1 galactosemia. What is known about the acute and long-term outcomes of these patients, therefore, is based on very limited data. Here, we present a study comparing acute and long-term outcomes of 12 patients homozygous for S135L, 25 patients compound heterozygous for S135L, and 105 patients homozygous for two GALT-null (G) alleles. This is the largest cohort of S135L patients characterized to date. Acute disease following milk exposure in the newborn period was common among patients in all 3 comparison groups in our study, as were long-term complications in the domains of speech, cognition, and motor outcomes. In contrast, while at least 80% of both GALT-null and S135L compound heterozygous girls and women showed evidence of an adverse ovarian outcome, prevalence was only 25% among S135L homozygotes. Further, all young women in this study with even one copy of S135L achieved spontaneous menarche; this is true for only about 33% of women with classic galactosemia. Overall, we observed that while most long-term outcomes trended milder among groups of patients with even one copy of S135L, many individual patients, either homozygous or compound heterozygous for S135L, nonetheless experienced long-term outcomes that were not mild. This was true despite detection by newborn screening and both early and life-long dietary restriction of galactose. This information should empower more evidence-based counseling for galactosemia patients with S135L.
publishDate 2022
dc.date.none.fl_str_mv 2022-11
2022-11-01T00:00:00Z
2023-10-09T14:32:54Z
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/10400.17/4715
url http://hdl.handle.net/10400.17/4715
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv J Inherit Metab Dis . 2022 Nov;45(6):1106-1117.
10.1002/jimd.12556
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.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
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
instname_str 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
repository.mail.fl_str_mv
_version_ 1799133620646969344