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Long-Term Follow-Up of Three Family Members with a Novel NNT Pathogenic Variant Causing Primary Adrenal Insufficiency

Nicotinamide nucleotide transhydrogenase (NNT) deficiency causes primary adrenal insufficiency (PAI) and possibly some extra-adrenal manifestations. A limited number of these patients were previously described. We present the clinical and genetic characteristics of three family members with a bialle...

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Autores principales: Krasovec, Tjasa, Sikonja, Jaka, Zerjav Tansek, Mojca, Debeljak, Marusa, Ilovar, Sasa, Trebusak Podkrajsek, Katarina, Bertok, Sara, Tesovnik, Tine, Kovac, Jernej, Suput Omladic, Jasna, Hartmann, Michaela F., Wudy, Stefan A., Avbelj Stefanija, Magdalena, Battelino, Tadej, Kotnik, Primoz, Groselj, Urh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9140979/
https://www.ncbi.nlm.nih.gov/pubmed/35627102
http://dx.doi.org/10.3390/genes13050717
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author Krasovec, Tjasa
Sikonja, Jaka
Zerjav Tansek, Mojca
Debeljak, Marusa
Ilovar, Sasa
Trebusak Podkrajsek, Katarina
Bertok, Sara
Tesovnik, Tine
Kovac, Jernej
Suput Omladic, Jasna
Hartmann, Michaela F.
Wudy, Stefan A.
Avbelj Stefanija, Magdalena
Battelino, Tadej
Kotnik, Primoz
Groselj, Urh
author_facet Krasovec, Tjasa
Sikonja, Jaka
Zerjav Tansek, Mojca
Debeljak, Marusa
Ilovar, Sasa
Trebusak Podkrajsek, Katarina
Bertok, Sara
Tesovnik, Tine
Kovac, Jernej
Suput Omladic, Jasna
Hartmann, Michaela F.
Wudy, Stefan A.
Avbelj Stefanija, Magdalena
Battelino, Tadej
Kotnik, Primoz
Groselj, Urh
author_sort Krasovec, Tjasa
collection PubMed
description Nicotinamide nucleotide transhydrogenase (NNT) deficiency causes primary adrenal insufficiency (PAI) and possibly some extra-adrenal manifestations. A limited number of these patients were previously described. We present the clinical and genetic characteristics of three family members with a biallelic novel pathogenic variant in the NNT gene. The patients were followed until the ages of 21.6, 20.2, and 4.2 years. PAI was diagnosed in the eldest two brothers after an Addisonian crisis and the third was diagnosed at the age of 4.5 months in the asymptomatic stage due to the genetic screening of family members. Whole exome sequencing with a targeted interpretation of variants in genes related to PAI was performed in all the patients. The urinary steroid metabolome was determined by gas chromatography–mass spectrometry in the asymptomatic patient. The three patients, who were homozygous for c.1575dup in the NNT gene, developed isolated glucocorticoid deficiency. The urinary steroid metabolome showed normal excretion of cortisol metabolites. The adolescent patients had slow pubertal progression with low–normal testicular volume, while testicular endocrine function was normal. Bone mineral density was in the range for osteopenia in both grown-up siblings. Echocardiography revealed no structural or functional heart abnormalities. This article is among the first with a comprehensive and chronologically-detailed description of patients with NNT deficiency.
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spelling pubmed-91409792022-05-28 Long-Term Follow-Up of Three Family Members with a Novel NNT Pathogenic Variant Causing Primary Adrenal Insufficiency Krasovec, Tjasa Sikonja, Jaka Zerjav Tansek, Mojca Debeljak, Marusa Ilovar, Sasa Trebusak Podkrajsek, Katarina Bertok, Sara Tesovnik, Tine Kovac, Jernej Suput Omladic, Jasna Hartmann, Michaela F. Wudy, Stefan A. Avbelj Stefanija, Magdalena Battelino, Tadej Kotnik, Primoz Groselj, Urh Genes (Basel) Article Nicotinamide nucleotide transhydrogenase (NNT) deficiency causes primary adrenal insufficiency (PAI) and possibly some extra-adrenal manifestations. A limited number of these patients were previously described. We present the clinical and genetic characteristics of three family members with a biallelic novel pathogenic variant in the NNT gene. The patients were followed until the ages of 21.6, 20.2, and 4.2 years. PAI was diagnosed in the eldest two brothers after an Addisonian crisis and the third was diagnosed at the age of 4.5 months in the asymptomatic stage due to the genetic screening of family members. Whole exome sequencing with a targeted interpretation of variants in genes related to PAI was performed in all the patients. The urinary steroid metabolome was determined by gas chromatography–mass spectrometry in the asymptomatic patient. The three patients, who were homozygous for c.1575dup in the NNT gene, developed isolated glucocorticoid deficiency. The urinary steroid metabolome showed normal excretion of cortisol metabolites. The adolescent patients had slow pubertal progression with low–normal testicular volume, while testicular endocrine function was normal. Bone mineral density was in the range for osteopenia in both grown-up siblings. Echocardiography revealed no structural or functional heart abnormalities. This article is among the first with a comprehensive and chronologically-detailed description of patients with NNT deficiency. MDPI 2022-04-20 /pmc/articles/PMC9140979/ /pubmed/35627102 http://dx.doi.org/10.3390/genes13050717 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Krasovec, Tjasa
Sikonja, Jaka
Zerjav Tansek, Mojca
Debeljak, Marusa
Ilovar, Sasa
Trebusak Podkrajsek, Katarina
Bertok, Sara
Tesovnik, Tine
Kovac, Jernej
Suput Omladic, Jasna
Hartmann, Michaela F.
Wudy, Stefan A.
Avbelj Stefanija, Magdalena
Battelino, Tadej
Kotnik, Primoz
Groselj, Urh
Long-Term Follow-Up of Three Family Members with a Novel NNT Pathogenic Variant Causing Primary Adrenal Insufficiency
title Long-Term Follow-Up of Three Family Members with a Novel NNT Pathogenic Variant Causing Primary Adrenal Insufficiency
title_full Long-Term Follow-Up of Three Family Members with a Novel NNT Pathogenic Variant Causing Primary Adrenal Insufficiency
title_fullStr Long-Term Follow-Up of Three Family Members with a Novel NNT Pathogenic Variant Causing Primary Adrenal Insufficiency
title_full_unstemmed Long-Term Follow-Up of Three Family Members with a Novel NNT Pathogenic Variant Causing Primary Adrenal Insufficiency
title_short Long-Term Follow-Up of Three Family Members with a Novel NNT Pathogenic Variant Causing Primary Adrenal Insufficiency
title_sort long-term follow-up of three family members with a novel nnt pathogenic variant causing primary adrenal insufficiency
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9140979/
https://www.ncbi.nlm.nih.gov/pubmed/35627102
http://dx.doi.org/10.3390/genes13050717
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