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...

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Autores principales: Pereira-Nunes, Joana, Ferreras, Cristina, Grangeia, Ana, Aguiar, Francisca, Rodrigues, Mariana, Brito, Iva
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cureus 2023
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.
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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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