Long-Term Follow-Up of Three Family Members with a Novel <i>NNT</i> 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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| Format: | Article |
| Language: | English |
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MDPI AG
2022-04-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/13/5/717 |
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| author | Tjasa Krasovec Jaka Sikonja Mojca Zerjav Tansek Marusa Debeljak Sasa Ilovar Katarina Trebusak Podkrajsek Sara Bertok Tine Tesovnik Jernej Kovac Jasna Suput Omladic Michaela F. Hartmann Stefan A. Wudy Magdalena Avbelj Stefanija Tadej Battelino Primoz Kotnik Urh Groselj |
| author_facet | Tjasa Krasovec Jaka Sikonja Mojca Zerjav Tansek Marusa Debeljak Sasa Ilovar Katarina Trebusak Podkrajsek Sara Bertok Tine Tesovnik Jernej Kovac Jasna Suput Omladic Michaela F. Hartmann Stefan A. Wudy Magdalena Avbelj Stefanija Tadej Battelino Primoz Kotnik Urh Groselj |
| author_sort | Tjasa Krasovec |
| collection | DOAJ |
| 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 <i>NNT</i> 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 <i>NNT</i> 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. |
| first_indexed | 2024-03-10T03:50:45Z |
| format | Article |
| id | doaj.art-e762fdb0582c47ba970e3668db86faa5 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T03:50:45Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-e762fdb0582c47ba970e3668db86faa52023-11-23T11:08:21ZengMDPI AGGenes2073-44252022-04-0113571710.3390/genes13050717Long-Term Follow-Up of Three Family Members with a Novel <i>NNT</i> Pathogenic Variant Causing Primary Adrenal InsufficiencyTjasa Krasovec0Jaka Sikonja1Mojca Zerjav Tansek2Marusa Debeljak3Sasa Ilovar4Katarina Trebusak Podkrajsek5Sara Bertok6Tine Tesovnik7Jernej Kovac8Jasna Suput Omladic9Michaela F. Hartmann10Stefan A. Wudy11Magdalena Avbelj Stefanija12Tadej Battelino13Primoz Kotnik14Urh Groselj15Faculty of Medicine, University of Ljubljana, Vrazov Trg 2, SI-1000 Ljubljana, SloveniaFaculty of Medicine, University of Ljubljana, Vrazov Trg 2, SI-1000 Ljubljana, SloveniaFaculty of Medicine, University of Ljubljana, Vrazov Trg 2, SI-1000 Ljubljana, SloveniaClinical Institute of Special Laboratory Diagnostics, University Children’s Hospital, University Medical Centre Ljubljana, Vrazov Trg 1, SI-1000 Ljubljana, SloveniaDepartment of Pediatric Cardiology, University Children’s Hospital, University Medical Centre Ljubljana, Bohoriceva Ulica 20, SI-1000 Ljubljana, SloveniaFaculty of Medicine, University of Ljubljana, Vrazov Trg 2, SI-1000 Ljubljana, SloveniaDepartment of Endocrinology, Diabetes, and Metabolic Diseases, University Children’s Hospital, University Medical Centre Ljubljana, Bohoriceva Ulica 20, SI-1000 Ljubljana, SloveniaClinical Institute of Special Laboratory Diagnostics, University Children’s Hospital, University Medical Centre Ljubljana, Vrazov Trg 1, SI-1000 Ljubljana, SloveniaFaculty of Medicine, University of Ljubljana, Vrazov Trg 2, SI-1000 Ljubljana, SloveniaFaculty of Medicine, University of Ljubljana, Vrazov Trg 2, SI-1000 Ljubljana, SloveniaLaboratory for Translational Hormone Analytics, Steroid Research and Mass Spectrometry Unit, Division of Pediatric Endocrinology and Diabetology, Center of Child and Adolescent Medicine, Justus Liebig University, Feulgenstraße 12, 35392 Giessen, GermanyLaboratory for Translational Hormone Analytics, Steroid Research and Mass Spectrometry Unit, Division of Pediatric Endocrinology and Diabetology, Center of Child and Adolescent Medicine, Justus Liebig University, Feulgenstraße 12, 35392 Giessen, GermanyFaculty of Medicine, University of Ljubljana, Vrazov Trg 2, SI-1000 Ljubljana, SloveniaFaculty of Medicine, University of Ljubljana, Vrazov Trg 2, SI-1000 Ljubljana, SloveniaFaculty of Medicine, University of Ljubljana, Vrazov Trg 2, SI-1000 Ljubljana, SloveniaFaculty of Medicine, University of Ljubljana, Vrazov Trg 2, SI-1000 Ljubljana, SloveniaNicotinamide 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 <i>NNT</i> 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 <i>NNT</i> 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.https://www.mdpi.com/2073-4425/13/5/717nicotinamide nucleotide transhydrogenaseNNT deficiencyprimary adrenal insufficiencynucleotide duplicationhearth sonographypubertal development |
| spellingShingle | Tjasa Krasovec Jaka Sikonja Mojca Zerjav Tansek Marusa Debeljak Sasa Ilovar Katarina Trebusak Podkrajsek Sara Bertok Tine Tesovnik Jernej Kovac Jasna Suput Omladic Michaela F. Hartmann Stefan A. Wudy Magdalena Avbelj Stefanija Tadej Battelino Primoz Kotnik Urh Groselj Long-Term Follow-Up of Three Family Members with a Novel <i>NNT</i> Pathogenic Variant Causing Primary Adrenal Insufficiency Genes nicotinamide nucleotide transhydrogenase NNT deficiency primary adrenal insufficiency nucleotide duplication hearth sonography pubertal development |
| title | Long-Term Follow-Up of Three Family Members with a Novel <i>NNT</i> Pathogenic Variant Causing Primary Adrenal Insufficiency |
| title_full | Long-Term Follow-Up of Three Family Members with a Novel <i>NNT</i> Pathogenic Variant Causing Primary Adrenal Insufficiency |
| title_fullStr | Long-Term Follow-Up of Three Family Members with a Novel <i>NNT</i> Pathogenic Variant Causing Primary Adrenal Insufficiency |
| title_full_unstemmed | Long-Term Follow-Up of Three Family Members with a Novel <i>NNT</i> Pathogenic Variant Causing Primary Adrenal Insufficiency |
| title_short | Long-Term Follow-Up of Three Family Members with a Novel <i>NNT</i> Pathogenic Variant Causing Primary Adrenal Insufficiency |
| title_sort | long term follow up of three family members with a novel i nnt i pathogenic variant causing primary adrenal insufficiency |
| topic | nicotinamide nucleotide transhydrogenase NNT deficiency primary adrenal insufficiency nucleotide duplication hearth sonography pubertal development |
| url | https://www.mdpi.com/2073-4425/13/5/717 |
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