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Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C.
Pelletier, Félixe; Perrier, Stefanie; Cayami, Ferdy K; Mirchi, Amytice; Saikali, Stephan; Tran, Luan T; Ulrick, Nicole; Guerrero, Kether; Rampakakis, Emmanouil; van Spaendonk, Rosalina M L; Naidu, Sakkubai; Pohl, Daniela; Gibson, William T; Demos, Michelle; Goizet, Cyril; Tejera-Martin, Ingrid; Potic, Ana; Fogel, Brent L; Brais, Bernard; Sylvain, Michel; Sébire, Guillaume; Lourenço, Charles Marques; Bonkowsky, Joshua L; Catsman-Berrevoets, Coriene; Pinto, Pedro S; Tirupathi, Sandya; Strømme, Petter; de Grauw, Ton; Gieruszczak-Bialek, Dorota; Krägeloh-Mann, Ingeborg; Mierzewska, Hanna; Philippi, Heike; Rankin, Julia; Atik, Tahir; Banwell, Brenda; Benko, William S; Blaschek, Astrid; Bley, Annette; Boltshauser, Eugen; Bratkovic, Drago; Brozova, Klara; Cimas, Icíar; Clough, Christopher; Corenblum, Bernard; Dinopoulos, Argirios; Dolan, Gail; Faletra, Flavio; Fernandez, Raymond; Fletcher, Janice; Garcia Garcia, Maria Eugenia.
Afiliação
  • Pelletier F; Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.
  • Perrier S; Department of Pediatrics, McGill University, Montreal, QC, Canada.
  • Cayami FK; Department of Human Genetics, McGill University, Montreal, QC, Canada.
  • Mirchi A; Child Health and Human Development Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
  • Saikali S; Department of Specialized Medicine, Division of Medical Genetics, McGill University Health Centre, Montreal, QC, Canada.
  • Tran LT; Division of Child Neurology, Department of Pediatrics, CHU Sainte-Justine, Université de Montréal, Montreal, QC, Canada.
  • Ulrick N; Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.
  • Guerrero K; Child Health and Human Development Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
  • Rampakakis E; Department of Child Neurology, Amsterdam Leukodystrophy Center, Emma Children's Hospital, Amsterdam University Medical Centers, and Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
  • van Spaendonk RML; Center of Biomedical Research, Faculty of Medicine, Diponegoro University, Semarang, Indonesia.
  • Naidu S; Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.
  • Pohl D; Department of Pediatrics, McGill University, Montreal, QC, Canada.
  • Gibson WT; Department of Human Genetics, McGill University, Montreal, QC, Canada.
  • Demos M; Child Health and Human Development Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
  • Goizet C; Department of Specialized Medicine, Division of Medical Genetics, McGill University Health Centre, Montreal, QC, Canada.
  • Tejera-Martin I; Department of Pathology, Centre Hospitalier Universitaire de Québec, Québec City, QC, Canada.
  • Potic A; Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.
  • Fogel BL; Department of Pediatrics, McGill University, Montreal, QC, Canada.
  • Brais B; Department of Human Genetics, McGill University, Montreal, QC, Canada.
  • Sylvain M; Child Health and Human Development Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
  • Sébire G; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Lourenço CM; Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.
  • Bonkowsky JL; Department of Pediatrics, McGill University, Montreal, QC, Canada.
  • Catsman-Berrevoets C; Department of Human Genetics, McGill University, Montreal, QC, Canada.
  • Pinto PS; Child Health and Human Development Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
  • Tirupathi S; Department of Pediatrics, McGill University, Montreal, QC, Canada.
  • Strømme P; Department of Clinical Genetics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
  • de Grauw T; Department of Neurogenetics, Kennedy Krieger Institute, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
  • Gieruszczak-Bialek D; Division of Neurology, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada.
  • Krägeloh-Mann I; Department of Medical Genetics, University of British Columbia, BC Children's Hospital Research Institute, Vancouver, BC, Canada.
  • Mierzewska H; Division of Neurology, Department of Pediatrics, University of British Columbia, BC Children's Hospital, Vancouver, BC, Canada.
  • Philippi H; Centre de Référence Neurogénétique, Service de Génétique Médicale, Bordeaux University Hospital, and Laboratoire MRGM, INSERM U1211, Université de Bordeaux, Bordeaux, France.
  • Rankin J; Department of Neurology, Hospital Universitario Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Canary Islands, Spain.
  • Atik T; Department of Neurology, Clinic for Child Neurology and Psychiatry, Medical Faculty University of Belgrade, Belgrade, Serbia.
  • Banwell B; Departments of Neurology and Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
  • Benko WS; Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.
  • Blaschek A; Department of Human Genetics, McGill University, Montreal, QC, Canada.
  • Bley A; Montreal Neurological Institute, Montreal, QC, Canada.
  • Boltshauser E; Centre Mère Enfant, CHU de Québec, Québec City, QC, Canada.
  • Bratkovic D; Department of Pediatrics, McGill University, Montreal, QC, Canada.
  • Brozova K; Department of Pediatrics, Université de Sherbrooke, Sherbrooke, QC, Canada.
  • Cimas I; Faculdade de Medicina, Centro Universitario Estácio de Ribeirão Preto, Ribeirão Preto, SP, Brazil.
  • Clough C; Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, USA.
  • Corenblum B; Department of Paediatric Neurology, Erasmus University Hospital - Sophia Children's Hospital, 3015 CN Rotterdam, The Netherlands.
  • Dinopoulos A; Neuroradiology Department, Centro Hospitalar do Porto, Porto, Portugal.
  • Dolan G; Department of Paediatric Neurology, Royal Belfast Hospital for Sick Children, Belfast, UK.
  • Faletra F; Division of Pediatrics and Adolescent Medicine, Oslo University Hospital, Ullevål, 0450 Oslo, and University of Oslo, Oslo, Norway.
  • Fernandez R; Department of Pediatrics, Emory School of Medicine, Atlanta, GA, USA.
  • Fletcher J; Department of Medical Genetics, Children's Memorial Health Institute, Warsaw, Poland.
  • Garcia Garcia ME; Department of Pediatrics, Medical University of Warsaw, Warsaw, Poland.
J Clin Endocrinol Metab ; 106(2): e660-e674, 2021 01 23.
Article em En | MEDLINE | ID: mdl-33005949
ABSTRACT
CONTEXT 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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: RNA Polimerases Dirigidas por DNA / Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central / Doenças Mitocondriais / Doenças do Sistema Endócrino / Transtornos do Crescimento Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prevalence_studies / Risk_factors_studies Limite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Infant / Male / Newborn Idioma: En Ano de publicação: 2021 Tipo de documento: Article
Texto completo
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Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: RNA Polimerases Dirigidas por DNA / Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central / Doenças Mitocondriais / Doenças do Sistema Endócrino / Transtornos do Crescimento Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prevalence_studies / Risk_factors_studies Limite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Infant / Male / Newborn Idioma: En Ano de publicação: 2021 Tipo de documento: Article