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

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Standard

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; Sebire, 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; Gasparini, Paolo; Gburek-Augustat, Janina; Gonzalez Moron, Dolores; Hamati, Aline; Harting, Inga; Hertzberg, Christoph; Hill, Alan; Hobson, Grace M; Innes, A Micheil; Kauffman, Marcelo; Kirwin, Susan M; Kluger, Gerhard; Kolditz, Petra; Kotzaeridou, Urania; La Piana, Roberta; Liston, Eriskay; McClintock, William; McEntagart, Meriel; McKenzie, Fiona; Melançon, Serge; Misbahuddin, Anjum; Suri, Mohnish; Monton, Fernando I; Moutton, Sebastien; Murphy, Raymond P J; Nickel, Miriam; Onay, Hüseyin; Orcesi, Simona; Özkınay, Ferda; Patzer, Steffi; Pedro, Helio; Pekic, Sandra; Pineda Marfa, Mercedes; Pizzino, Amy; Plecko, Barbara; Poll-The, Bwee Tien; Popovic, Vera; Rating, Dietz; Rioux, Marie-France; Rodriguez Espinosa, Norberto; Ronan, Anne; Ostergaard, John R; Rossignol, Elsa; Sanchez-Carpintero, Rocio; Schossig, Anna; Senbil, Nesrin; Sønderberg Roos, Laura K; Stevens, Cathy A; Synofzik, Matthis; Sztriha, László; Tibussek, Daniel; Timmann, Dagmar; Tonduti, Davide; van de Warrenburg, Bart P; Vázquez-López, Maria; Venkateswaran, Sunita; Wasling, Pontus; Wassmer, Evangeline; Webster, Richard I; Wiegand, Gert; Yoon, Grace; Rotteveel, Joost; Schiffmann, Raphael; van der Knaap, Marjo; Vanderver, Adeline; Martos-Moreno, Gabriel Á; Polychronakos, Constantin; Wolf, Nicole I; Bernard, Geneviève.

I: The Journal of clinical endocrinology and metabolism, Bind 106, Nr. 2, 02.2021, s. e660-e674.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

Pelletier, F, Perrier, S, Cayami, FK, Mirchi, A, Saikali, S, Tran, LT, Ulrick, N, Guerrero, K, Rampakakis, E, van Spaendonk, RML, Naidu, S, Pohl, D, Gibson, WT, Demos, M, Goizet, C, Tejera-Martin, I, Potic, A, Fogel, BL, Brais, B, Sylvain, M, Sebire, G, Lourenço, CM, Bonkowsky, JL, Catsman-Berrevoets, C, Pinto, PS, Tirupathi, S, Strømme, P, de Grauw, T, Gieruszczak-Bialek, D, Krägeloh-Mann, I, Mierzewska, H, Philippi, H, Rankin, J, Atik, T, Banwell, B, Benko, WS, Blaschek, A, Bley, A, Boltshauser, E, Bratkovic, D, Brozova, K, Cimas, I, Clough, C, Corenblum, B, Dinopoulos, A, Dolan, G, Faletra, F, Fernandez, R, Fletcher, J, Garcia Garcia, ME, Gasparini, P, Gburek-Augustat, J, Gonzalez Moron, D, Hamati, A, Harting, I, Hertzberg, C, Hill, A, Hobson, GM, Innes, AM, Kauffman, M, Kirwin, SM, Kluger, G, Kolditz, P, Kotzaeridou, U, La Piana, R, Liston, E, McClintock, W, McEntagart, M, McKenzie, F, Melançon, S, Misbahuddin, A, Suri, M, Monton, FI, Moutton, S, Murphy, RPJ, Nickel, M, Onay, H, Orcesi, S, Özkınay, F, Patzer, S, Pedro, H, Pekic, S, Pineda Marfa, M, Pizzino, A, Plecko, B, Poll-The, BT, Popovic, V, Rating, D, Rioux, M-F, Rodriguez Espinosa, N, Ronan, A, Ostergaard, JR, Rossignol, E, Sanchez-Carpintero, R, Schossig, A, Senbil, N, Sønderberg Roos, LK, Stevens, CA, Synofzik, M, Sztriha, L, Tibussek, D, Timmann, D, Tonduti, D, van de Warrenburg, BP, Vázquez-López, M, Venkateswaran, S, Wasling, P, Wassmer, E, Webster, RI, Wiegand, G, Yoon, G, Rotteveel, J, Schiffmann, R, van der Knaap, M, Vanderver, A, Martos-Moreno, GÁ, Polychronakos, C, Wolf, NI & Bernard, G 2021, 'Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C', The Journal of clinical endocrinology and metabolism, bind 106, nr. 2, s. e660-e674. https://doi.org/10.1210/clinem/dgaa700

APA

Pelletier, F., Perrier, S., Cayami, F. K., Mirchi, A., Saikali, S., Tran, L. T., Ulrick, N., Guerrero, K., Rampakakis, E., van Spaendonk, R. M. L., Naidu, S., Pohl, D., Gibson, W. T., Demos, M., Goizet, C., Tejera-Martin, I., Potic, A., Fogel, B. L., Brais, B., ... Bernard, G. (2021). Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C. The Journal of clinical endocrinology and metabolism, 106(2), e660-e674. https://doi.org/10.1210/clinem/dgaa700

CBE

Pelletier F, Perrier S, Cayami FK, Mirchi A, Saikali S, Tran LT, Ulrick N, Guerrero K, Rampakakis E, van Spaendonk RML, Naidu S, Pohl D, Gibson WT, Demos M, Goizet C, Tejera-Martin I, Potic A, Fogel BL, Brais B, Sylvain M, Sebire G, Lourenço CM, Bonkowsky JL, Catsman-Berrevoets C, Pinto PS, Tirupathi S, Strømme P, de Grauw T, Gieruszczak-Bialek D, Krägeloh-Mann I, Mierzewska H, Philippi H, Rankin J, Atik T, Banwell B, Benko WS, Blaschek A, Bley A, Boltshauser E, Bratkovic D, Brozova K, Cimas I, Clough C, Corenblum B, Dinopoulos A, Dolan G, Faletra F, Fernandez R, Fletcher J, Garcia Garcia ME, Gasparini P, Gburek-Augustat J, Gonzalez Moron D, Hamati A, Harting I, Hertzberg C, Hill A, Hobson GM, Innes AM, Kauffman M, Kirwin SM, Kluger G, Kolditz P, Kotzaeridou U, La Piana R, Liston E, McClintock W, McEntagart M, McKenzie F, Melançon S, Misbahuddin A, Suri M, Monton FI, Moutton S, Murphy RPJ, Nickel M, Onay H, Orcesi S, Özkınay F, Patzer S, Pedro H, Pekic S, Pineda Marfa M, Pizzino A, Plecko B, Poll-The BT, Popovic V, Rating D, Rioux M-F, Rodriguez Espinosa N, Ronan A, Ostergaard JR, Rossignol E, Sanchez-Carpintero R, Schossig A, Senbil N, Sønderberg Roos LK, Stevens CA, Synofzik M, Sztriha L, Tibussek D, Timmann D, Tonduti D, van de Warrenburg BP, Vázquez-López M, Venkateswaran S, Wasling P, Wassmer E, Webster RI, Wiegand G, Yoon G, Rotteveel J, Schiffmann R, van der Knaap M, Vanderver A, Martos-Moreno GÁ, Polychronakos C, Wolf NI, Bernard G. 2021. Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C. The Journal of clinical endocrinology and metabolism. 106(2):e660-e674. https://doi.org/10.1210/clinem/dgaa700

MLA

Pelletier, Félixe o.a.. "Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C". The Journal of clinical endocrinology and metabolism. 2021, 106(2). e660-e674. https://doi.org/10.1210/clinem/dgaa700

Vancouver

Pelletier F, Perrier S, Cayami FK, Mirchi A, Saikali S, Tran LT o.a. Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C. The Journal of clinical endocrinology and metabolism. 2021 feb;106(2):e660-e674. https://doi.org/10.1210/clinem/dgaa700

Author

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 ; Sebire, 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 ; Gasparini, Paolo ; Gburek-Augustat, Janina ; Gonzalez Moron, Dolores ; Hamati, Aline ; Harting, Inga ; Hertzberg, Christoph ; Hill, Alan ; Hobson, Grace M ; Innes, A Micheil ; Kauffman, Marcelo ; Kirwin, Susan M ; Kluger, Gerhard ; Kolditz, Petra ; Kotzaeridou, Urania ; La Piana, Roberta ; Liston, Eriskay ; McClintock, William ; McEntagart, Meriel ; McKenzie, Fiona ; Melançon, Serge ; Misbahuddin, Anjum ; Suri, Mohnish ; Monton, Fernando I ; Moutton, Sebastien ; Murphy, Raymond P J ; Nickel, Miriam ; Onay, Hüseyin ; Orcesi, Simona ; Özkınay, Ferda ; Patzer, Steffi ; Pedro, Helio ; Pekic, Sandra ; Pineda Marfa, Mercedes ; Pizzino, Amy ; Plecko, Barbara ; Poll-The, Bwee Tien ; Popovic, Vera ; Rating, Dietz ; Rioux, Marie-France ; Rodriguez Espinosa, Norberto ; Ronan, Anne ; Ostergaard, John R ; Rossignol, Elsa ; Sanchez-Carpintero, Rocio ; Schossig, Anna ; Senbil, Nesrin ; Sønderberg Roos, Laura K ; Stevens, Cathy A ; Synofzik, Matthis ; Sztriha, László ; Tibussek, Daniel ; Timmann, Dagmar ; Tonduti, Davide ; van de Warrenburg, Bart P ; Vázquez-López, Maria ; Venkateswaran, Sunita ; Wasling, Pontus ; Wassmer, Evangeline ; Webster, Richard I ; Wiegand, Gert ; Yoon, Grace ; Rotteveel, Joost ; Schiffmann, Raphael ; van der Knaap, Marjo ; Vanderver, Adeline ; Martos-Moreno, Gabriel Á ; Polychronakos, Constantin ; Wolf, Nicole I ; Bernard, Geneviève. / Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C. I: The Journal of clinical endocrinology and metabolism. 2021 ; Bind 106, Nr. 2. s. e660-e674.

Bibtex

@article{ffa054e59d1b4c479e78a12bfdef6b36,
title = "Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C",
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.",
author = "F{\'e}lixe Pelletier and Stefanie Perrier and Cayami, {Ferdy K} and Amytice Mirchi and Stephan Saikali and Tran, {Luan T} and Nicole Ulrick and Kether Guerrero and Emmanouil Rampakakis and {van Spaendonk}, {Rosalina M L} and Sakkubai Naidu and Daniela Pohl and Gibson, {William T} and Michelle Demos and Cyril Goizet and Ingrid Tejera-Martin and Ana Potic and Fogel, {Brent L} and Bernard Brais and Michel Sylvain and Guillaume Sebire and Louren{\c c}o, {Charles Marques} and Bonkowsky, {Joshua L} and Coriene Catsman-Berrevoets and Pinto, {Pedro S} and Sandya Tirupathi and Petter Str{\o}mme and {de Grauw}, Ton and Dorota Gieruszczak-Bialek and Ingeborg Kr{\"a}geloh-Mann and Hanna Mierzewska and Heike Philippi and Julia Rankin and Tahir Atik and Brenda Banwell and Benko, {William S} and Astrid Blaschek and Annette Bley and Eugen Boltshauser and Drago Bratkovic and Klara Brozova and Ic{\'i}ar Cimas and Christopher Clough and Bernard Corenblum and Argirios Dinopoulos and Gail Dolan and Flavio Faletra and Raymond Fernandez and Janice Fletcher and {Garcia Garcia}, {Maria Eugenia} and Paolo Gasparini and Janina Gburek-Augustat and {Gonzalez Moron}, Dolores and Aline Hamati and Inga Harting and Christoph Hertzberg and Alan Hill and Hobson, {Grace M} and Innes, {A Micheil} and Marcelo Kauffman and Kirwin, {Susan M} and Gerhard Kluger and Petra Kolditz and Urania Kotzaeridou and {La Piana}, Roberta and Eriskay Liston and William McClintock and Meriel McEntagart and Fiona McKenzie and Serge Melan{\c c}on and Anjum Misbahuddin and Mohnish Suri and Monton, {Fernando I} and Sebastien Moutton and Murphy, {Raymond P J} and Miriam Nickel and H{\"u}seyin Onay and Simona Orcesi and Ferda {\"O}zkınay and Steffi Patzer and Helio Pedro and Sandra Pekic and {Pineda Marfa}, Mercedes and Amy Pizzino and Barbara Plecko and Poll-The, {Bwee Tien} and Vera Popovic and Dietz Rating and Marie-France Rioux and {Rodriguez Espinosa}, Norberto and Anne Ronan and Ostergaard, {John R} and Elsa Rossignol and Rocio Sanchez-Carpintero and Anna Schossig and Nesrin Senbil and {S{\o}nderberg Roos}, {Laura K} and Stevens, {Cathy A} and Matthis Synofzik and L{\'a}szl{\'o} Sztriha and Daniel Tibussek and Dagmar Timmann and Davide Tonduti and {van de Warrenburg}, {Bart P} and Maria V{\'a}zquez-L{\'o}pez and Sunita Venkateswaran and Pontus Wasling and Evangeline Wassmer and Webster, {Richard I} and Gert Wiegand and Grace Yoon and Joost Rotteveel and Raphael Schiffmann and {van der Knaap}, Marjo and Adeline Vanderver and Martos-Moreno, {Gabriel {\'A}} and Constantin Polychronakos and Wolf, {Nicole I} and Genevi{\`e}ve Bernard",
note = "{\textcopyright} The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society.",
year = "2021",
month = feb,
doi = "10.1210/clinem/dgaa700",
language = "English",
volume = "106",
pages = "e660--e674",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "Oxford University Press",
number = "2",

}

RIS

TY - JOUR

T1 - Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C

AU - Pelletier, Félixe

AU - Perrier, Stefanie

AU - Cayami, Ferdy K

AU - Mirchi, Amytice

AU - Saikali, Stephan

AU - Tran, Luan T

AU - Ulrick, Nicole

AU - Guerrero, Kether

AU - Rampakakis, Emmanouil

AU - van Spaendonk, Rosalina M L

AU - Naidu, Sakkubai

AU - Pohl, Daniela

AU - Gibson, William T

AU - Demos, Michelle

AU - Goizet, Cyril

AU - Tejera-Martin, Ingrid

AU - Potic, Ana

AU - Fogel, Brent L

AU - Brais, Bernard

AU - Sylvain, Michel

AU - Sebire, Guillaume

AU - Lourenço, Charles Marques

AU - Bonkowsky, Joshua L

AU - Catsman-Berrevoets, Coriene

AU - Pinto, Pedro S

AU - Tirupathi, Sandya

AU - Strømme, Petter

AU - de Grauw, Ton

AU - Gieruszczak-Bialek, Dorota

AU - Krägeloh-Mann, Ingeborg

AU - Mierzewska, Hanna

AU - Philippi, Heike

AU - Rankin, Julia

AU - Atik, Tahir

AU - Banwell, Brenda

AU - Benko, William S

AU - Blaschek, Astrid

AU - Bley, Annette

AU - Boltshauser, Eugen

AU - Bratkovic, Drago

AU - Brozova, Klara

AU - Cimas, Icíar

AU - Clough, Christopher

AU - Corenblum, Bernard

AU - Dinopoulos, Argirios

AU - Dolan, Gail

AU - Faletra, Flavio

AU - Fernandez, Raymond

AU - Fletcher, Janice

AU - Garcia Garcia, Maria Eugenia

AU - Gasparini, Paolo

AU - Gburek-Augustat, Janina

AU - Gonzalez Moron, Dolores

AU - Hamati, Aline

AU - Harting, Inga

AU - Hertzberg, Christoph

AU - Hill, Alan

AU - Hobson, Grace M

AU - Innes, A Micheil

AU - Kauffman, Marcelo

AU - Kirwin, Susan M

AU - Kluger, Gerhard

AU - Kolditz, Petra

AU - Kotzaeridou, Urania

AU - La Piana, Roberta

AU - Liston, Eriskay

AU - McClintock, William

AU - McEntagart, Meriel

AU - McKenzie, Fiona

AU - Melançon, Serge

AU - Misbahuddin, Anjum

AU - Suri, Mohnish

AU - Monton, Fernando I

AU - Moutton, Sebastien

AU - Murphy, Raymond P J

AU - Nickel, Miriam

AU - Onay, Hüseyin

AU - Orcesi, Simona

AU - Özkınay, Ferda

AU - Patzer, Steffi

AU - Pedro, Helio

AU - Pekic, Sandra

AU - Pineda Marfa, Mercedes

AU - Pizzino, Amy

AU - Plecko, Barbara

AU - Poll-The, Bwee Tien

AU - Popovic, Vera

AU - Rating, Dietz

AU - Rioux, Marie-France

AU - Rodriguez Espinosa, Norberto

AU - Ronan, Anne

AU - Ostergaard, John R

AU - Rossignol, Elsa

AU - Sanchez-Carpintero, Rocio

AU - Schossig, Anna

AU - Senbil, Nesrin

AU - Sønderberg Roos, Laura K

AU - Stevens, Cathy A

AU - Synofzik, Matthis

AU - Sztriha, László

AU - Tibussek, Daniel

AU - Timmann, Dagmar

AU - Tonduti, Davide

AU - van de Warrenburg, Bart P

AU - Vázquez-López, Maria

AU - Venkateswaran, Sunita

AU - Wasling, Pontus

AU - Wassmer, Evangeline

AU - Webster, Richard I

AU - Wiegand, Gert

AU - Yoon, Grace

AU - Rotteveel, Joost

AU - Schiffmann, Raphael

AU - van der Knaap, Marjo

AU - Vanderver, Adeline

AU - Martos-Moreno, Gabriel Á

AU - Polychronakos, Constantin

AU - Wolf, Nicole I

AU - Bernard, Geneviève

N1 - © The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society.

PY - 2021/2

Y1 - 2021/2

N2 - 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.

AB - 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.

U2 - 10.1210/clinem/dgaa700

DO - 10.1210/clinem/dgaa700

M3 - Journal article

C2 - 33005949

VL - 106

SP - e660-e674

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 2

ER -