Mevalonate Kinase Deficiency as Cause of Periodic Fever in Two Siblings

Correa, Alec Reginald Errol; Gupta, Neerja; Bagri, Narendra Kumar; Vignesh, Pandiarajan; Alam, Seema; Yamaguchi, Seiji

doi:10.1007/s13312-020-1742-9

Cited by 4 publications

(2 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The clinical heterogenicity of MKD is therefore well recognised. In addition, patients may often present with a variety of non-specific clinical manifestations mimicking other inflammatory or infectious disorders which can lead to diagnostic delay [7,8]. We report the case of a child presenting with vasculitis that was found by genetic testing to be caused by MKD thus highlighting the expanding spectrum of phenotypes associated with MKD and now adding this autoinflammatory disease to the ever-expanding list of causes of monogenic vasculitides [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

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

Omoyinmi¹,

Rowczenio²,

Sebire

et al. 2021

Pediatr Rheumatol

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

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

Omoyinmi¹,

Rowczenio²,

Sebire

et al. 2021

Pediatr Rheumatol

View full text Add to dashboard Cite

show abstract

“…It has been estimated that 75% of patients with HIDS were from Western Europe i.e. the Netherlands, France, and Italy [10][11][12], whereas only a small number of patients with HIDS have been reported from Asian countries [2,[13][14][15][16][17]. The prevalence of HIDS has been estimated to be in the range of 1:50,000 to 1:5000 [10].…”

Section: Introductionmentioning

confidence: 99%

Spectrum of clinical features and genetic variants in mevalonate kinase (MVK) gene of South Indian families suffering from Hyperimmunoglobulin D Syndrome

et al. 2020

View full text Add to dashboard Cite

Hyper-IgD syndrome (HIDS, OMIM #260920) is a rare autosomal recessive autoinflammatory disorder caused by pathogenic variants in the mevalonate kinase (MVK) gene. HIDS has an incidence of 1:50,000 to 1:5,000, and is thought to be prevalent mainly in northern Europe. Here, we report a case series of HIDS from India, which includes ten patients from six families who presented with a wide spectrum of clinical features such as recurrent fever, oral ulcers, rash, arthritis, recurrent diarrhea, hepatosplenomegaly, and high immunoglobulin levels. Using whole exome sequencing (WES) and/or Sanger capillary sequencing, we identified five distinct genetic variants in the MVK gene from nine patients belonging to six families. The variants were classified as pathogenic or likely pathogenic as per the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) guidelines for annotation of sequence variants. Over 70% of patients in the present study had two recurrent mutations in MVK gene i.e. a nonsynonymous variant p. V377I, popularly known as the 'Dutch mutation', along with a splicing variant c.226+2delT in a compound heterozygous form. Identity by descent analysis in two patients with the recurrent variants identified a 6.7 MB long haplotype suggesting a founder effect in the South Indian population. Our analysis suggests that a limited number of variants account for the majority of the patients with HIDS in South India. This has implications in clinical diagnosis, as well as in the development of cost-effective approaches for genetic diagnosis and

show abstract