Vasculitis in a patient with mevalonate kinase deficiency (MKD): a case report.
Biopsy
Child, Preschool
DNA
/ genetics
DNA Mutational Analysis
Delayed Diagnosis
Diagnosis, Differential
Genetic Testing
Genotype
Humans
Male
Mevalonate Kinase Deficiency
/ complications
Mutation
Phenotype
Phosphotransferases (Alcohol Group Acceptor)
/ genetics
Skin
/ pathology
Vasculitis
/ diagnosis
Autoinflammation
Cutaneous vasculitis
IL-1 blockade
Mevalonate kinase deficiency
Next-generation sequencing
Journal
Pediatric rheumatology online journal
ISSN: 1546-0096
Titre abrégé: Pediatr Rheumatol Online J
Pays: England
ID NLM: 101248897
Informations de publication
Date de publication:
22 Nov 2021
22 Nov 2021
Historique:
received:
27
05
2021
accepted:
21
10
2021
entrez:
23
11
2021
pubmed:
24
11
2021
medline:
15
3
2022
Statut:
epublish
Résumé
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. 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. 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.
Sections du résumé
BACKGROUND
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
METHODS
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
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.
Identifiants
pubmed: 34809655
doi: 10.1186/s12969-021-00645-8
pii: 10.1186/s12969-021-00645-8
pmc: PMC8607720
doi:
Substances chimiques
DNA
9007-49-2
Phosphotransferases (Alcohol Group Acceptor)
EC 2.7.1.-
mevalonate kinase
EC 2.7.1.36
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
161Subventions
Organisme : Versus Arthritis
ID : 21791 and 21593
Pays : United Kingdom
Informations de copyright
© 2021. The Author(s).
Références
Indian Pediatr. 2020 Feb 15;57(2):180-181
pubmed: 32060250
Hum Mol Genet. 1999 Aug;8(8):1523-8
pubmed: 10401001
Rheumatology (Oxford). 2021 Oct 2;60(10):4850-4854
pubmed: 33410495
Appl Clin Genet. 2016 Jul 20;9:101-10
pubmed: 27499643
Front Immunol. 2018 Nov 01;9:2524
pubmed: 30443255
Curr Rheumatol Rep. 2010 Apr;12(2):101-7
pubmed: 20425018
Front Immunol. 2018 Apr 11;9:735
pubmed: 29696024
Clin Exp Rheumatol. 2015 May-Jun;33(3):437-42
pubmed: 25897835
Arthritis Rheumatol. 2016 Nov;68(11):2795-2805
pubmed: 27213830
N Engl J Med. 2007 Jun 28;356(26):2700-3
pubmed: 17596604
Pediatr Rheumatol Online J. 2016 May 04;14(1):30
pubmed: 27142780
Rheumatol Int. 2018 Jan;38(1):13-24
pubmed: 29032440
Ann Rheum Dis. 2011 Dec;70(12):2155-8
pubmed: 21859689
Arch Dermatol. 1994 Jan;130(1):59-65
pubmed: 8285741
N Engl J Med. 2018 May 17;378(20):1908-1919
pubmed: 29768139
Nat Genet. 1999 Jun;22(2):178-81
pubmed: 10369262
Orphanet J Rare Dis. 2006 Apr 26;1:13
pubmed: 16722536