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Siblings With HNF4A Congenital Hyperinsulinism From Possible Parental Gonadal Mosaicism
Congenital hyperinsulinism is the most common cause of persistent hypoglycemia in early infancy. Mutations in the gene for heterozygous hepatocyte nuclear transcription factor 4-alpha (HNF4A) account for approximately 5% of cases and are inherited in an autosomal dominant fashion or arise as de novo...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10580462/ https://www.ncbi.nlm.nih.gov/pubmed/37908999 http://dx.doi.org/10.1210/jcemcr/luad089 |
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author | Wolschendorf, Robin Eimicke, Toni Swartz, Jonathan |
author_facet | Wolschendorf, Robin Eimicke, Toni Swartz, Jonathan |
author_sort | Wolschendorf, Robin |
collection | PubMed |
description | Congenital hyperinsulinism is the most common cause of persistent hypoglycemia in early infancy. Mutations in the gene for heterozygous hepatocyte nuclear transcription factor 4-alpha (HNF4A) account for approximately 5% of cases and are inherited in an autosomal dominant fashion or arise as de novo mutations. This case describes a unique presentation of parental gonadal, or germline, mosaicism as the suspected inheritance pattern for siblings with congenital hyperinsulinism caused by HNF4A mutations. Two siblings presented with hypoglycemia in the first hours of life and were subsequently confirmed to have hyperinsulinism. In each patient, glycemic control was achieved at relatively low doses of diazoxide. Both siblings tested positive for the same HNF4A mutation, whereas the parents tested negative for HNF4A mutations. Gonadal, or germline, mosaicism became the presumed leading diagnosis, given 2 unaffected parents with 2 children with congenital hyperinsulinism. The older sibling demonstrated additional clinical features of liver disease and renal Fanconi syndrome, both of which are associated with HNF4A mutations. Genetic testing plays an important role in the diagnosis and management of congenital hyperinsulinism. HNF4A mutations may arise by a range of mechanisms, including gonadal, or germline, mosaicism. HNF4A mutations have phenotypic variance that may affect multiple organ systems at any age. |
format | Online Article Text |
id | pubmed-10580462 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-105804622023-10-31 Siblings With HNF4A Congenital Hyperinsulinism From Possible Parental Gonadal Mosaicism Wolschendorf, Robin Eimicke, Toni Swartz, Jonathan JCEM Case Rep Case Report Congenital hyperinsulinism is the most common cause of persistent hypoglycemia in early infancy. Mutations in the gene for heterozygous hepatocyte nuclear transcription factor 4-alpha (HNF4A) account for approximately 5% of cases and are inherited in an autosomal dominant fashion or arise as de novo mutations. This case describes a unique presentation of parental gonadal, or germline, mosaicism as the suspected inheritance pattern for siblings with congenital hyperinsulinism caused by HNF4A mutations. Two siblings presented with hypoglycemia in the first hours of life and were subsequently confirmed to have hyperinsulinism. In each patient, glycemic control was achieved at relatively low doses of diazoxide. Both siblings tested positive for the same HNF4A mutation, whereas the parents tested negative for HNF4A mutations. Gonadal, or germline, mosaicism became the presumed leading diagnosis, given 2 unaffected parents with 2 children with congenital hyperinsulinism. The older sibling demonstrated additional clinical features of liver disease and renal Fanconi syndrome, both of which are associated with HNF4A mutations. Genetic testing plays an important role in the diagnosis and management of congenital hyperinsulinism. HNF4A mutations may arise by a range of mechanisms, including gonadal, or germline, mosaicism. HNF4A mutations have phenotypic variance that may affect multiple organ systems at any age. Oxford University Press 2023-08-14 /pmc/articles/PMC10580462/ /pubmed/37908999 http://dx.doi.org/10.1210/jcemcr/luad089 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Case Report Wolschendorf, Robin Eimicke, Toni Swartz, Jonathan Siblings With HNF4A Congenital Hyperinsulinism From Possible Parental Gonadal Mosaicism |
title | Siblings With HNF4A Congenital Hyperinsulinism From Possible Parental Gonadal Mosaicism |
title_full | Siblings With HNF4A Congenital Hyperinsulinism From Possible Parental Gonadal Mosaicism |
title_fullStr | Siblings With HNF4A Congenital Hyperinsulinism From Possible Parental Gonadal Mosaicism |
title_full_unstemmed | Siblings With HNF4A Congenital Hyperinsulinism From Possible Parental Gonadal Mosaicism |
title_short | Siblings With HNF4A Congenital Hyperinsulinism From Possible Parental Gonadal Mosaicism |
title_sort | siblings with hnf4a congenital hyperinsulinism from possible parental gonadal mosaicism |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10580462/ https://www.ncbi.nlm.nih.gov/pubmed/37908999 http://dx.doi.org/10.1210/jcemcr/luad089 |
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