SRD5A3-CDG: Emerging Phenotypic Features of an Ultrarare CDG Subtype

Background: SRD5A3-CDG is a rare N-glycosylation defect caused by steroid 5 alpha reductase type 3 deficiency. Its key feature is an early severe visual impairment with variable ocular anomalies often leading to diagnosis. Additional symptoms are still poorly defined. In this case study, we discuss...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Nazreen Kamarus Jaman, Preeya Rehsi, Robert H. Henderson, Ulrike Löbel, Kshitij Mankad, Stephanie Grunewald
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	SRD5A3-CDG steroid 5 alpha reductase deficiency emerging phenotypic features retinal dystrophy congenital disorder of glycosylation CDG Genetics QH426-470
Acceso en línea:	https://doaj.org/article/2c1a32e28fbe4d858ef21bf2008b43ac
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:2c1a32e28fbe4d858ef21bf2008b43ac
record_format	dspace
spelling	oai:doaj.org-article:2c1a32e28fbe4d858ef21bf2008b43ac2021-12-01T23:41:09ZSRD5A3-CDG: Emerging Phenotypic Features of an Ultrarare CDG Subtype1664-802110.3389/fgene.2021.737094https://doaj.org/article/2c1a32e28fbe4d858ef21bf2008b43ac2021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fgene.2021.737094/fullhttps://doaj.org/toc/1664-8021Background: SRD5A3-CDG is a rare N-glycosylation defect caused by steroid 5 alpha reductase type 3 deficiency. Its key feature is an early severe visual impairment with variable ocular anomalies often leading to diagnosis. Additional symptoms are still poorly defined. In this case study, we discuss 11 genetically confirmed cases, and report on emerging features involving other systems in addition to the eye phenotype.Methods: In total, 11 SRD5A3-CDG patients in five sets of sibships were included in the study. Data on 9 of 11 patients are as of yet unpublished. Patients’ results on biochemical and genetic investigations and on in-depth phenotyping are presented.Results: Key diagnostic features of SRD5A3-CDG are ophthalmological abnormalities with early-onset retinal dystrophy and optic nerve hypoplasia. SRD5A3-CDG is also characterized by variable neurological symptoms including intellectual disability, ataxia, and hypotonia. Furthermore, ichthyosiform skin lesions, joint laxity, and scoliosis have been observed in our cohort. We also report additional findings including dystonia, anxiety disorder, gastrointestinal symptoms, and MRI findings of small basal ganglia and mal-rotated hippocampus, whereas previous publications described dysmorphic features as a common finding in SRD5A3, which could not be confirmed in our patient cohort.Conclusion: The detailed description of the phenotype of this large cohort of patients with SRD5A3-CDG highlights that the key clinical diagnostic features of SRD5A3-CDG are an early onset form of ophthalmological problems in patients with a multisystem disorder with variable symptoms evolving over time. This should aid earlier diagnosis and confirms the need for long-time follow-up of patients.Nazreen Kamarus JamanPreeya RehsiRobert H. HendersonRobert H. HendersonUlrike LöbelKshitij MankadStephanie GrunewaldStephanie GrunewaldFrontiers Media S.A.articleSRD5A3-CDGsteroid 5 alpha reductase deficiencyemerging phenotypic featuresretinal dystrophycongenital disorder of glycosylationCDGGeneticsQH426-470ENFrontiers in Genetics, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	SRD5A3-CDG steroid 5 alpha reductase deficiency emerging phenotypic features retinal dystrophy congenital disorder of glycosylation CDG Genetics QH426-470
spellingShingle	SRD5A3-CDG steroid 5 alpha reductase deficiency emerging phenotypic features retinal dystrophy congenital disorder of glycosylation CDG Genetics QH426-470 Nazreen Kamarus Jaman Preeya Rehsi Robert H. Henderson Robert H. Henderson Ulrike Löbel Kshitij Mankad Stephanie Grunewald Stephanie Grunewald SRD5A3-CDG: Emerging Phenotypic Features of an Ultrarare CDG Subtype
description	Background: SRD5A3-CDG is a rare N-glycosylation defect caused by steroid 5 alpha reductase type 3 deficiency. Its key feature is an early severe visual impairment with variable ocular anomalies often leading to diagnosis. Additional symptoms are still poorly defined. In this case study, we discuss 11 genetically confirmed cases, and report on emerging features involving other systems in addition to the eye phenotype.Methods: In total, 11 SRD5A3-CDG patients in five sets of sibships were included in the study. Data on 9 of 11 patients are as of yet unpublished. Patients’ results on biochemical and genetic investigations and on in-depth phenotyping are presented.Results: Key diagnostic features of SRD5A3-CDG are ophthalmological abnormalities with early-onset retinal dystrophy and optic nerve hypoplasia. SRD5A3-CDG is also characterized by variable neurological symptoms including intellectual disability, ataxia, and hypotonia. Furthermore, ichthyosiform skin lesions, joint laxity, and scoliosis have been observed in our cohort. We also report additional findings including dystonia, anxiety disorder, gastrointestinal symptoms, and MRI findings of small basal ganglia and mal-rotated hippocampus, whereas previous publications described dysmorphic features as a common finding in SRD5A3, which could not be confirmed in our patient cohort.Conclusion: The detailed description of the phenotype of this large cohort of patients with SRD5A3-CDG highlights that the key clinical diagnostic features of SRD5A3-CDG are an early onset form of ophthalmological problems in patients with a multisystem disorder with variable symptoms evolving over time. This should aid earlier diagnosis and confirms the need for long-time follow-up of patients.
format	article
author	Nazreen Kamarus Jaman Preeya Rehsi Robert H. Henderson Robert H. Henderson Ulrike Löbel Kshitij Mankad Stephanie Grunewald Stephanie Grunewald
author_facet	Nazreen Kamarus Jaman Preeya Rehsi Robert H. Henderson Robert H. Henderson Ulrike Löbel Kshitij Mankad Stephanie Grunewald Stephanie Grunewald
author_sort	Nazreen Kamarus Jaman
title	SRD5A3-CDG: Emerging Phenotypic Features of an Ultrarare CDG Subtype
title_short	SRD5A3-CDG: Emerging Phenotypic Features of an Ultrarare CDG Subtype
title_full	SRD5A3-CDG: Emerging Phenotypic Features of an Ultrarare CDG Subtype
title_fullStr	SRD5A3-CDG: Emerging Phenotypic Features of an Ultrarare CDG Subtype
title_full_unstemmed	SRD5A3-CDG: Emerging Phenotypic Features of an Ultrarare CDG Subtype
title_sort	srd5a3-cdg: emerging phenotypic features of an ultrarare cdg subtype
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/2c1a32e28fbe4d858ef21bf2008b43ac
work_keys_str_mv	AT nazreenkamarusjaman srd5a3cdgemergingphenotypicfeaturesofanultrararecdgsubtype AT preeyarehsi srd5a3cdgemergingphenotypicfeaturesofanultrararecdgsubtype AT roberthhenderson srd5a3cdgemergingphenotypicfeaturesofanultrararecdgsubtype AT roberthhenderson srd5a3cdgemergingphenotypicfeaturesofanultrararecdgsubtype AT ulrikelobel srd5a3cdgemergingphenotypicfeaturesofanultrararecdgsubtype AT kshitijmankad srd5a3cdgemergingphenotypicfeaturesofanultrararecdgsubtype AT stephaniegrunewald srd5a3cdgemergingphenotypicfeaturesofanultrararecdgsubtype AT stephaniegrunewald srd5a3cdgemergingphenotypicfeaturesofanultrararecdgsubtype
_version_	1718403973521604608

SRD5A3-CDG: Emerging Phenotypic Features of an Ultrarare CDG Subtype

Ejemplares similares