Two Siblings With Recurrent Fevers: The Path to Mevalonate Kinase Deficiency Diagnosis
Systemic autoinflammatory diseases (SAIDs) are a group of disorders that constitute a rare cause of recurrent fevers. Recurrent fevers are defined as periodic febrile episodes lasting from days to weeks, separated by symptom-free intervals of variable duration. They present multiple etiologies, repr...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cureus
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9911135/ https://www.ncbi.nlm.nih.gov/pubmed/36788924 http://dx.doi.org/10.7759/cureus.33613 |
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author | Pereira-Nunes, Joana Ferreras, Cristina Grangeia, Ana Aguiar, Francisca Rodrigues, Mariana Brito, Iva |
author_facet | Pereira-Nunes, Joana Ferreras, Cristina Grangeia, Ana Aguiar, Francisca Rodrigues, Mariana Brito, Iva |
author_sort | Pereira-Nunes, Joana |
collection | PubMed |
description | Systemic autoinflammatory diseases (SAIDs) are a group of disorders that constitute a rare cause of recurrent fevers. Recurrent fevers are defined as periodic febrile episodes lasting from days to weeks, separated by symptom-free intervals of variable duration. They present multiple etiologies, representing a diagnostic challenge. Mevalonate kinase deficiency (MKD) is a genetic SAID, a rare hereditary recurrent fever syndrome (HRF) caused by pathogenic variants in the mevalonate kinase (MVK) gene. It is characterized by the early onset of periodic fever flares, frequently associated with joint, gastrointestinal, skin, and lymph node involvement. Although elevated serum immunoglobulin D (IgD) levels were previously considered an MKD's hallmark, normal values do not exclude it. High serum immunoglobulin A (IgA) is frequent. An acute-phase response and elevated urinary mevalonic acid (UAV) excretion during flares may aid in the diagnosis. Genetic testing is an essential tool to confirm the diagnosis. The authors report two siblings presenting with early infancy onset of recurrent febrile illness and characteristic associated symptoms, one of which was initially misdiagnosed with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome. MKD diagnoses were only established at 12 and nine years old, respectively, after the identification of the same two MVKgene variants. The diagnosis in the eldest favored the earlier recognition of MKD in the youngest. Owing to its wide spectrum of manifestations, with many being nonspecific and/or shared with other more frequent entities, a significant proportion of MKD patients present a long delay until its final establishment. These cases illustrate the MKD diagnosis and management's difficulties, reinforcing the importance of a careful clinical history and HRF awareness for its prompt diagnosis and appropriate precocious referral. |
format | Online Article Text |
id | pubmed-9911135 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cureus |
record_format | MEDLINE/PubMed |
spelling | pubmed-99111352023-02-13 Two Siblings With Recurrent Fevers: The Path to Mevalonate Kinase Deficiency Diagnosis Pereira-Nunes, Joana Ferreras, Cristina Grangeia, Ana Aguiar, Francisca Rodrigues, Mariana Brito, Iva Cureus Family/General Practice Systemic autoinflammatory diseases (SAIDs) are a group of disorders that constitute a rare cause of recurrent fevers. Recurrent fevers are defined as periodic febrile episodes lasting from days to weeks, separated by symptom-free intervals of variable duration. They present multiple etiologies, representing a diagnostic challenge. Mevalonate kinase deficiency (MKD) is a genetic SAID, a rare hereditary recurrent fever syndrome (HRF) caused by pathogenic variants in the mevalonate kinase (MVK) gene. It is characterized by the early onset of periodic fever flares, frequently associated with joint, gastrointestinal, skin, and lymph node involvement. Although elevated serum immunoglobulin D (IgD) levels were previously considered an MKD's hallmark, normal values do not exclude it. High serum immunoglobulin A (IgA) is frequent. An acute-phase response and elevated urinary mevalonic acid (UAV) excretion during flares may aid in the diagnosis. Genetic testing is an essential tool to confirm the diagnosis. The authors report two siblings presenting with early infancy onset of recurrent febrile illness and characteristic associated symptoms, one of which was initially misdiagnosed with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome. MKD diagnoses were only established at 12 and nine years old, respectively, after the identification of the same two MVKgene variants. The diagnosis in the eldest favored the earlier recognition of MKD in the youngest. Owing to its wide spectrum of manifestations, with many being nonspecific and/or shared with other more frequent entities, a significant proportion of MKD patients present a long delay until its final establishment. These cases illustrate the MKD diagnosis and management's difficulties, reinforcing the importance of a careful clinical history and HRF awareness for its prompt diagnosis and appropriate precocious referral. Cureus 2023-01-10 /pmc/articles/PMC9911135/ /pubmed/36788924 http://dx.doi.org/10.7759/cureus.33613 Text en Copyright © 2023, Pereira-Nunes et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Family/General Practice Pereira-Nunes, Joana Ferreras, Cristina Grangeia, Ana Aguiar, Francisca Rodrigues, Mariana Brito, Iva Two Siblings With Recurrent Fevers: The Path to Mevalonate Kinase Deficiency Diagnosis |
title | Two Siblings With Recurrent Fevers: The Path to Mevalonate Kinase Deficiency Diagnosis |
title_full | Two Siblings With Recurrent Fevers: The Path to Mevalonate Kinase Deficiency Diagnosis |
title_fullStr | Two Siblings With Recurrent Fevers: The Path to Mevalonate Kinase Deficiency Diagnosis |
title_full_unstemmed | Two Siblings With Recurrent Fevers: The Path to Mevalonate Kinase Deficiency Diagnosis |
title_short | Two Siblings With Recurrent Fevers: The Path to Mevalonate Kinase Deficiency Diagnosis |
title_sort | two siblings with recurrent fevers: the path to mevalonate kinase deficiency diagnosis |
topic | Family/General Practice |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9911135/ https://www.ncbi.nlm.nih.gov/pubmed/36788924 http://dx.doi.org/10.7759/cureus.33613 |
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