Skip to main content
SpringerLink
Log in

Mevalonate Kinase Deficiency (MKD)/Hyperimmunoglobulin D Syndrome (HIDS)

  • Chapter
  • First Online:
Book cover Auto-Inflammatory Syndromes

  • 993 Accesses

Abstract

Mevalonate kinase deficiency (MKD) and its milder spectrum hyper IgD syndrome (HIDS) is a rare monogenic disease with multiple organ manifestations. HIDS patients most commonly present with recurrent febrile attacks, gastrointestinal symptoms (abdominal pain, nausea, and vomiting), inflammatory arthritis, and arthralgia as well as mucocutaneous manifestations. Disease usually manifests in childhood, although adult cases of HIDS have been described in literature.

The most common mutation in MKD is pV377I (G1129A) and is primarily observed among heterozygous individuals with HIDS. Other genetic mutations have also been described in literature, but not all of them seem to correlate with clinical manifestations.

Increased levels of immunoglobulin D (IgD) as well as high levels of IL-1, IL-6, and tumor necrosis factor-α (TNFα) are usually observed in majority of the patients during febrile attacks.

New treatment modalities have been developed based on recent advances in pathogenesis of MKD/HIDS. Stemming from the proposed mechanism of inflammasome activation, IL-1 pathway appears to be the most effective therapeutic target to date.

Early diagnosis and treatment are crucial in MKD/HIDS as it can prevent irreversible organ damage and improve quality of life of patients, whose daily activities, education, and employment are often affected by frequent febrile attacks.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Rowe DS, Fahey JL. A New Class of Human Immunoglobulins. I. A Unique Myeloma Protein. J Exp Med. 1965;121:171–84.

    Article  CAS  Google Scholar 

  2. Drenth JP, et al. Location of the gene causing hyperimmunoglobulinemia D and periodic fever syndrome differs from that for familial Mediterranean fever. International Hyper-IgD Study Group. Hum Genet. 1994;94(6):616–20.

    Article  CAS  Google Scholar 

  3. Church LD, et al. Hereditary auto-inflammatory disorders and biologics. Springer Semin Immunopathol. 2006;27(4):494–508.

    Article  CAS  Google Scholar 

  4. Durel CA, et al. Observational study of a French and Belgian multicenter cohort of 23 patients diagnosed in adulthood with mevalonate kinase deficiency. Medicine (Baltimore). 2016;95(11):e3027.

    Article  CAS  Google Scholar 

  5. Toplak N, et al. Periodic fever syndromes in Eastern and Central European countries: results of a pediatric multinational survey. Pediatr Rheumatol Online J. 2010;8:29.

    Article  Google Scholar 

  6. Stoffels M, Simon A. Hyper-IgD syndrome or mevalonate kinase deficiency. Curr Opin Rheumatol. 2011;23(5):419–23.

    Article  CAS  Google Scholar 

  7. Drenth JP, van der Meer JW. Hereditary periodic fever. N Engl J Med. 2001;345(24):1748–57.

    Article  CAS  Google Scholar 

  8. Caso F, et al. Working the endless puzzle of hereditary autoinflammatory disorders. Mod Rheumatol. 2014;24(3):381–9.

    Article  CAS  Google Scholar 

  9. Simon A, et al. A founder effect in the hyperimmunoglobulinemia D and periodic fever syndrome. Am J Med. 2003;114(2):148–52.

    Article  CAS  Google Scholar 

  10. Houten SM, et al. Carrier frequency of the V377I (1129G>A) MVK mutation, associated with Hyper-IgD and periodic fever syndrome, in the Netherlands. Eur J Hum Genet. 2003;11(2):196–200.

    Article  CAS  Google Scholar 

  11. Hospach T, et al. Pseudodominant inheritance of the hyperimmunoglobulinemia D with periodic fever syndrome in a mother and her two monozygotic twins. Arthritis Rheum. 2005;52(11):3606–10.

    Article  CAS  Google Scholar 

  12. van der Hilst JC, et al. Long-term follow-up, clinical features, and quality of life in a series of 103 patients with hyperimmunoglobulinemia D syndrome. Medicine (Baltimore). 2008;87(6):301–10.

    Article  Google Scholar 

  13. Ter Haar NM, et al. The phenotype and genotype of mevalonate kinase deficiency: a series of 114 cases from the Eurofever registry. Arthritis Rheumatol. 2016;68(11):2795–805.

    Article  Google Scholar 

  14. Edwards PA, Ericsson J. Sterols and isoprenoids: signaling molecules derived from the cholesterol biosynthetic pathway. Annu Rev Biochem. 1999;68:157–85.

    Article  CAS  Google Scholar 

  15. Nagashima T, et al. Apoptosis of rheumatoid synovial cells by statins through the blocking of protein geranylgeranylation: a potential therapeutic approach to rheumatoid arthritis. Arthritis Rheum. 2006;54(2):579–86.

    Article  CAS  Google Scholar 

  16. Simon A, et al. Simvastatin treatment for inflammatory attacks of the hyperimmunoglobulinemia D and periodic fever syndrome. Clin Pharmacol Ther. 2004;75(5):476–83.

    Article  CAS  Google Scholar 

  17. Henneman L, et al. Compromised geranylgeranylation of RhoA and Rac1 in mevalonate kinase deficiency. J Inherit Metab Dis. 2010;33(5):625–32.

    Article  CAS  Google Scholar 

  18. Kostjukovits S, et al. Treatment of hyperimmunoglobulinemia D syndrome with biologics in children: review of the literature and Finnish experience. Eur J Pediatr. 2015;174(6):707–14.

    Article  Google Scholar 

  19. Stoffels M, et al. TLR2/TLR4-dependent exaggerated cytokine production in hyperimmunoglobulinaemia D and periodic fever syndrome. Rheumatology (Oxford). 2015;54(2):363–8.

    Article  CAS  Google Scholar 

  20. Bader-Meunier B, et al. Mevalonate kinase deficiency: a survey of 50 patients. Pediatrics. 2011;128(1):e152–9.

    Article  Google Scholar 

  21. Balgobind B, Wittebol-Post D, Frenkel J. Retinitis pigmentosa in mevalonate kinase deficiency. J Inherit Metab Dis. 2005;28(6):1143–5.

    Article  CAS  Google Scholar 

  22. Obici L, et al. First report of systemic reactive (AA) amyloidosis in a patient with the hyperimmunoglobulinemia D with periodic fever syndrome. Arthritis Rheum. 2004;50(9):2966–9.

    Article  Google Scholar 

  23. Damian LO, et al. Ultrasonographic findings in hyperimmunoglobulin D syndrome: a case report. Med Ultrason. 2017;19(2):224–7.

    Article  Google Scholar 

  24. Tsimaratos M, et al. Crescentic glomerulonephritis in hyper IgD syndrome. Pediatr Nephrol. 1999;13(2):132–4.

    Article  CAS  Google Scholar 

  25. de Hullu JA, et al. Hyper-IgD syndrome and pregnancy. Eur J Obstet Gynecol Reprod Biol. 1996;68(1–2):223–5.

    Article  Google Scholar 

  26. Drenth JP, Haagsma CJ, van der Meer JW. Hyperimmunoglobulinemia D and periodic fever syndrome. The clinical spectrum in a series of 50 patients. International Hyper-IgD Study Group. Medicine (Baltimore). 1994;73(3):133–44.

    Article  CAS  Google Scholar 

  27. Houten SM, et al. Mutations in MVK, encoding mevalonate kinase, cause hyperimmunoglobulinaemia D and periodic fever syndrome. Nat Genet. 1999;22(2):175–7.

    Article  CAS  Google Scholar 

  28. Schneiders MS, et al. Manipulation of isoprenoid biosynthesis as a possible therapeutic option in mevalonate kinase deficiency. Arthritis Rheum. 2006;54(7):2306–13.

    Article  CAS  Google Scholar 

  29. Ter Haar N, et al. Treatment of autoinflammatory diseases: results from the Eurofever registry and a literature review. Ann Rheum Dis. 2013;72(5):678–85.

    Article  Google Scholar 

  30. Ozen S, Demir S. Monogenic periodic fever syndromes: treatment options for the pediatric patient. Paediatr Drugs. 2017;19(4):303–11.

    Article  Google Scholar 

  31. Bodar EJ, et al. Effect of etanercept and anakinra on inflammatory attacks in the hyper-IgD syndrome: introducing a vaccination provocation model. Neth J Med. 2005;63(7):260–4.

    CAS  PubMed  Google Scholar 

  32. Arostegui JI, et al. Open-label, phase II study to assess the efficacy and safety of Canakinumab treatment in active Hyperimmunoglobulinemia D with periodic fever syndrome. Arthritis Rheumatol. 2017;69(8):1679–88.

    Article  CAS  Google Scholar 

  33. Shendi HM, Devlin LA, Edgar JD. Interleukin 6 blockade for hyperimmunoglobulin D and periodic fever syndrome. J Clin Rheumatol. 2014;20(2):103–5.

    Article  Google Scholar 

  34. Musters A, et al. Anti-interleukin 6 receptor therapy for hyper-IgD syndrome. BMJ Case Rep. 2015;2015. ISSN 1757-790X.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. NYU School of Medicine, Rheumatology Division/Department of Internal Medicine, New York, NY, USA

    Olga Petryna

  2. New York Presbyterian Hospital, Department of Internal Medicine, Brooklyn, NY, USA

    Neha Purat

Authors
  1. Olga Petryna
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Neha Purat
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Olga Petryna .

Editor information

Editors and Affiliations

  1. New York University School of Medicine, New York, NY, USA

    Petros Efthimiou

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Petryna, O., Purat, N. (2019). Mevalonate Kinase Deficiency (MKD)/Hyperimmunoglobulin D Syndrome (HIDS). In: Efthimiou, P. (eds) Auto-Inflammatory Syndromes. Springer, Cham. https://doi.org/10.1007/978-3-319-96929-9_2

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-96929-9_2

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-96928-2

  • Online ISBN: 978-3-319-96929-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation