Vasculitis in a patient with mevalonate kinase deficiency (MKD): a case report

Abstract Background Mevalonate kinase deficiency (MKD) is a rare autoinflammatory condition caused by biallelic loss-of-function (LOF) mutations in mevalonate kinase (MVK) gene encoding the enzyme mevalonate kinase. Patients with MKD display a variety of non-specific clinical manifestations, which c...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ebun Omoyinmi, Dorota Rowczenio, Neil Sebire, Paul A. Brogan, Despina Eleftheriou
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Mevalonate kinase deficiency Autoinflammation Cutaneous vasculitis Next-generation sequencing IL-1 blockade Pediatrics RJ1-570 Diseases of the musculoskeletal system RC925-935
Acceso en línea:	https://doaj.org/article/6526b0dfe00b45159b766f0e2519ef01
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:6526b0dfe00b45159b766f0e2519ef01
record_format	dspace
spelling	oai:doaj.org-article:6526b0dfe00b45159b766f0e2519ef012021-11-28T12:04:44ZVasculitis in a patient with mevalonate kinase deficiency (MKD): a case report10.1186/s12969-021-00645-81546-0096https://doaj.org/article/6526b0dfe00b45159b766f0e2519ef012021-11-01T00:00:00Zhttps://doi.org/10.1186/s12969-021-00645-8https://doaj.org/toc/1546-0096Abstract Background Mevalonate kinase deficiency (MKD) is a rare autoinflammatory condition caused by biallelic loss-of-function (LOF) mutations in mevalonate kinase (MVK) gene encoding the enzyme mevalonate kinase. Patients with MKD display a variety of non-specific clinical manifestations, which can lead to diagnostic delay. We report the case of a child presenting with vasculitis that was found by genetic testing to be caused by MKD, and now add this autoinflammatory disease to the ever-expanding list of causes of monogenic vasculitides. Case presentation A 2-year-old male presented with an acute 7-day history of high-grade fever, abdominal pain, diarrhoea, rectal bleeding and extensive purpuric and necrotic lesions, predominantly affecting the lower limbs. He had been suffering from recurrent episodes of fever from early in infancy, associated with maculopapular/petechial rashes triggered by intercurrent infection, and after vaccines. Extensive infection screen was negative. Skin biopsy revealed small vessel vasculitis. Visceral digital subtraction arteriography was normal. With a diagnosis of severe idiopathic cutaneous vasculitis, he was treated with corticosteroids and mycophenolate mofetil. Despite that his acute phase reactants remained elevated, fever persisted and the vasculitic lesions progressed. Next-generation sequencing revealed compound heterozygous mutation in MVK c.928G > A (p.V310M) and c.1129G > A (p.V377I) while reduced mevalonate enzyme activity was confirmed suggesting a diagnosis of MKD as a cause of the severe vasculitis. Prompt targeted treatment with IL-1 blockade was initiated preventing escalation to more toxic vasculitis therapies and reducing unnecessary exposure to cytotoxic treatment. Conclusions Our report highlights the broad clinical phenotype of MKD that includes severe cutaneous vasculitis and emphasizes the need to consider early genetic screening for young children presenting with vasculitis to exclude a monogenic vasculitis which may be amenable to targeted treatment.Ebun OmoyinmiDorota RowczenioNeil SebirePaul A. BroganDespina EleftheriouBMCarticleMevalonate kinase deficiencyAutoinflammationCutaneous vasculitisNext-generation sequencingIL-1 blockadePediatricsRJ1-570Diseases of the musculoskeletal systemRC925-935ENPediatric Rheumatology Online Journal, Vol 19, Iss 1, Pp 1-4 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Mevalonate kinase deficiency Autoinflammation Cutaneous vasculitis Next-generation sequencing IL-1 blockade Pediatrics RJ1-570 Diseases of the musculoskeletal system RC925-935
spellingShingle	Mevalonate kinase deficiency Autoinflammation Cutaneous vasculitis Next-generation sequencing IL-1 blockade Pediatrics RJ1-570 Diseases of the musculoskeletal system RC925-935 Ebun Omoyinmi Dorota Rowczenio Neil Sebire Paul A. Brogan Despina Eleftheriou Vasculitis in a patient with mevalonate kinase deficiency (MKD): a case report
description	Abstract Background Mevalonate kinase deficiency (MKD) is a rare autoinflammatory condition caused by biallelic loss-of-function (LOF) mutations in mevalonate kinase (MVK) gene encoding the enzyme mevalonate kinase. Patients with MKD display a variety of non-specific clinical manifestations, which can lead to diagnostic delay. We report the case of a child presenting with vasculitis that was found by genetic testing to be caused by MKD, and now add this autoinflammatory disease to the ever-expanding list of causes of monogenic vasculitides. Case presentation A 2-year-old male presented with an acute 7-day history of high-grade fever, abdominal pain, diarrhoea, rectal bleeding and extensive purpuric and necrotic lesions, predominantly affecting the lower limbs. He had been suffering from recurrent episodes of fever from early in infancy, associated with maculopapular/petechial rashes triggered by intercurrent infection, and after vaccines. Extensive infection screen was negative. Skin biopsy revealed small vessel vasculitis. Visceral digital subtraction arteriography was normal. With a diagnosis of severe idiopathic cutaneous vasculitis, he was treated with corticosteroids and mycophenolate mofetil. Despite that his acute phase reactants remained elevated, fever persisted and the vasculitic lesions progressed. Next-generation sequencing revealed compound heterozygous mutation in MVK c.928G > A (p.V310M) and c.1129G > A (p.V377I) while reduced mevalonate enzyme activity was confirmed suggesting a diagnosis of MKD as a cause of the severe vasculitis. Prompt targeted treatment with IL-1 blockade was initiated preventing escalation to more toxic vasculitis therapies and reducing unnecessary exposure to cytotoxic treatment. Conclusions Our report highlights the broad clinical phenotype of MKD that includes severe cutaneous vasculitis and emphasizes the need to consider early genetic screening for young children presenting with vasculitis to exclude a monogenic vasculitis which may be amenable to targeted treatment.
format	article
author	Ebun Omoyinmi Dorota Rowczenio Neil Sebire Paul A. Brogan Despina Eleftheriou
author_facet	Ebun Omoyinmi Dorota Rowczenio Neil Sebire Paul A. Brogan Despina Eleftheriou
author_sort	Ebun Omoyinmi
title	Vasculitis in a patient with mevalonate kinase deficiency (MKD): a case report
title_short	Vasculitis in a patient with mevalonate kinase deficiency (MKD): a case report
title_full	Vasculitis in a patient with mevalonate kinase deficiency (MKD): a case report
title_fullStr	Vasculitis in a patient with mevalonate kinase deficiency (MKD): a case report
title_full_unstemmed	Vasculitis in a patient with mevalonate kinase deficiency (MKD): a case report
title_sort	vasculitis in a patient with mevalonate kinase deficiency (mkd): a case report
publisher	BMC
publishDate	2021
url	https://doaj.org/article/6526b0dfe00b45159b766f0e2519ef01
work_keys_str_mv	AT ebunomoyinmi vasculitisinapatientwithmevalonatekinasedeficiencymkdacasereport AT dorotarowczenio vasculitisinapatientwithmevalonatekinasedeficiencymkdacasereport AT neilsebire vasculitisinapatientwithmevalonatekinasedeficiencymkdacasereport AT paulabrogan vasculitisinapatientwithmevalonatekinasedeficiencymkdacasereport AT despinaeleftheriou vasculitisinapatientwithmevalonatekinasedeficiencymkdacasereport
_version_	1718408201732358144

Vasculitis in a patient with mevalonate kinase deficiency (MKD): a case report

Ejemplares similares