Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C

Basit Öğe Kaydı
dc.authoridMartos-Moreno, Gabriel Angel/0000-0001-5524-2646
dc.authoridRossignol, Elsa/0000-0002-9304-9385
dc.authoridKirwin, Susan/0000-0003-2008-4654
dc.authoridTran, Luan T/0000-0003-4666-1755
dc.authoridSaikali, Stephan/0000-0002-6966-7538
dc.authoridATIK, TAHIR/0000-0002-1142-3872
dc.authoridFaletra, Flavio/0000-0003-1483-3612
dc.contributor.authorPelletier, Felixe
dc.contributor.authorPerrier, Stefanie
dc.contributor.authorCayami, Ferdy K.
dc.contributor.authorMirchi, Amytice
dc.contributor.authorSaikali, Stephan
dc.contributor.authorTran, Luan T.
dc.contributor.authorUlrick, Nicole
dc.date.accessioned2025-01-21T16:38:32Z
dc.date.available2025-01-21T16:38:32Z
dc.date.issued2021
dc.departmentKırıkkale Üniversitesi
dc.description.abstractContext 4H or POLR3-related leukodystrophy is an autosomal recessive disorder typically characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, caused by biallelic pathogenic variants in POLR3A, POLR3B, POLR1C, and POLR3K. The endocrine and growth abnormalities associated with this disorder have not been thoroughly investigated to date. Objective To systematically characterize endocrine abnormalities of patients with 4H leukodystrophy. Design An international cross-sectional study was performed on 150 patients with genetically confirmed 4H leukodystrophy between 2015 and 2016. Endocrine and growth abnormalities were evaluated, and neurological and other non-neurological features were reviewed. Potential genotype/phenotype associations were also investigated. Setting This was a multicenter retrospective study using information collected from 3 predominant centers. Patients A total of 150 patients with 4H leukodystrophy and pathogenic variants in POLR3A, POLR3B, or POLR1C were included. Main Outcome Measures Variables used to evaluate endocrine and growth abnormalities included pubertal history, hormone levels (estradiol, testosterone, stimulated LH and FSH, stimulated GH, IGF-I, prolactin, ACTH, cortisol, TSH, and T4), and height and head circumference charts. Results The most common endocrine abnormalities were delayed puberty (57/74; 77% overall, 64% in males, 89% in females) and short stature (57/93; 61%), when evaluated according to physician assessment. Abnormal thyroid function was reported in 22% (13/59) of patients. Conclusions Our results confirm pubertal abnormalities and short stature are the most common endocrine features seen in 4H leukodystrophy. However, we noted that endocrine abnormalities are typically underinvestigated in this patient population. A prospective study is required to formulate evidence-based recommendations for management of the endocrine manifestations of this disorder.
dc.description.sponsorshipCanadian Institutes of Health Research [201610PJT-377869, MOP-G2-341146-159133-BRIDG]; Fondation Les Amis d'Elliot; Leuco-Action; Fondation Lueur d'Espoir pour Ayden; Fondation le Tout pour Loo; Reseau de Medecine Genetique Appliquee of the Fonds de Recherche du Quebec-Sante; Compute Canada; Fonds de Recherche du Quebec en Sante (FRQS) Doctoral Scholarship; Fondation du Grand defi Pierre Lavoie Doctoral Scholarship; McGill Faculty of Medicine F. S.B. Miller Fellowship; Research Institute of the McGill University Health Centre Desjardins Studentship in Child Health Research; Directorate of Higher Education Overseas Scholarship-Dikti Scholarship, Ministry of National Education, Republic of Indonesia; CIHR [201603PJT-148695]; BC Children's Hospital Foundation through its intramural Investigator Grant Award Program (IGAP); National Institute for Neurological Disorders and Stroke [R01NS082094]; Jakob Kamens Chair in Translational Neurotherapeutics; Fonds de Recherche du Quebec-Sante (FRQS); Canadian Institutes of Health Research; European Reference Network for Rare Neurological Disorders (ERN-RND) [739510]
dc.description.sponsorshipThis study was supported by grants from the Canadian Institutes of Health Research (201610PJT-377869, MOP-G2-341146-159133-BRIDG), Fondation Les Amis d'Elliot, Leuco-Action, Fondation Lueur d'Espoir pour Ayden, Fondation le Tout pour Loo, and Reseau de Medecine Genetique Appliquee of the Fonds de Recherche du Quebec-Sante to G. Bernard. This research was enabled in part by support provided by Compute Canada (www.computecanada.ca).S.Perrier is supported by the Fonds de Recherche du Quebec en Sante (FRQS) Doctoral Scholarship, the Fondation du Grand defi Pierre Lavoie Doctoral Scholarship, the McGill Faculty of Medicine F. S.B. Miller Fellowship, and the Research Institute of the McGill University Health Centre Desjardins Studentship in Child Health Research. F. K.C. is a recipient of the Directorate of Higher Education Overseas Scholarship-Dikti Scholarship, Ministry of National Education, Republic of Indonesia. W.T. G. received funding from the CIHR (201603PJT-148695) and is supported by the BC Children's Hospital Foundation through its intramural Investigator Grant Award Program (IGAP). B.L. F. was supported by the National Institute for Neurological Disorders and Stroke (R01NS082094). A.V. receives funding from the Jakob Kamens Chair in Translational Neurotherapeutics. G. Bernard has received a Research Scholar Junior 1 award from the Fonds de Recherche du Quebec-Sante (FRQS) (2012-2016) and the New Investigator Salary Award from the Canadian Institutes of Health Research (2017-2022). I.K.M., M. Synofzik, D. Tonduti, B.P.v.d.W., M.S. V.d.K., and N.I.W. are members of the European Reference Network for Rare Neurological Disorders (ERN-RND), project ID 739510.
dc.identifier.doi10.1210/clinem/dgaa700
dc.identifier.endpageE674
dc.identifier.issn0021-972X
dc.identifier.issn1945-7197
dc.identifier.issue2
dc.identifier.pmid33005949
dc.identifier.startpageE660
dc.identifier.urihttps://doi.org/10.1210/clinem/dgaa700
dc.identifier.urihttps://hdl.handle.net/20.500.12587/24685
dc.identifier.volume106
dc.identifier.wosWOS:000759115900048
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherEndocrine Soc
dc.relation.ispartofJournal of Clinical Endocrinology & Metabolism
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_20241229
dc.subjectPOLR3-related leukodystrophy; 4H leukodystrophy; hypomyelination; hypogonadotropic hypogonadism
dc.titleEndocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C
dc.typeArticle

Dosyalar

Koleksiyon

WOS İndeksli Yayınlar Koleksiyonu
PubMed İndeksli Yayınlar Koleksiyonu