Hyper-IgD syndrome/mevalonate kinase deficiency: what is new?

C M Mulders-Manders,A Simon

doi:10.1007/s00281-015-0492-6

Abstract

Mevalonate kinase deficiency or hyper-IgD syndrome is a hereditary autoinflammatory syndrome caused by mutations in the mevalonate kinase gene. In this review, we will discuss new findings in this disorder that have been published in the last 2 years. This includes new insights into pathophysiology, treatment, and the clinical phenotype linked to the genetic defect.

Highlights

The hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) is an autoinflammatory disease characterized by recurrent episodes of fever, cervical lymphadenopathy, hepatomegaly, splenomegaly, abdominal pain, skin rash, arthralgia, and other inflammatory symptoms [1] accompanied by increased inflammatory markers such as C-reactive protein (CRP) and serum amyloid A (SAA)
Apart from the abovementioned clinical phenotype of HIDS, mevalonate kinase deficiency (MKD) can present as mevalonate aciduria, a severe disease characterized by neurologic involvement with psychomotor retardation, cerebellar ataxia, and facial dysmorphy besides the inflammatory symptoms, leading to early death
As there is no clear border between phenotypes, we will use the term mevalonate kinase deficiency, which encompasses both HIDS and mevalonate aciduria, to describe the disease in this paper

Summary

Introduction

The hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) is an autoinflammatory disease characterized by recurrent episodes of fever, cervical lymphadenopathy, hepatomegaly, splenomegaly, abdominal pain, skin rash, arthralgia, and other inflammatory symptoms [1] accompanied by increased inflammatory markers such as C-reactive protein (CRP) and serum amyloid A (SAA). Non-sterol isoprenoid end products are involved in the prenylation of proteins, where either a farnesyl group or a geranylgeranyl group is attached to a protein. This process is necessary for adequate protein function. The level of remaining mevalonate kinase enzyme activity in MKD determines the clinical phenotype. Apart from the abovementioned clinical phenotype of HIDS, MKD can present as mevalonate aciduria, a severe disease characterized by neurologic involvement with psychomotor retardation, cerebellar ataxia, and facial dysmorphy besides the inflammatory symptoms, leading to early death. As there is no clear border between phenotypes, we will use the term mevalonate kinase deficiency, which encompasses both HIDS and mevalonate aciduria, to describe the disease in this paper. We will discuss new findings in MKD that have been published between January 1, 2012 and December 31, 2014

What is new on the pathophysiological mechanism of MKD?

What is new on the treatment of mevalonate kinase deficiency?

Extending the spectrum of mevalonate kinase deficiency

Diseases without systemic inflammation

Conclusion