Definition
This is a rare genetic autoinflammatory disease.
​
Formerly known as hyper-IgD syndrome or HIDS, for hyper IgD syndrome, the current, correct name is "mevalonate kinase deficiency".
​
The term IgD syndrome should no longer be used, nor should immunoglobulin D levels be measured in the blood, as they are non-specific.
Epidemiology
Its exact prevalence is unknown, but it is estimated that there are around a hundred cases in France.
It affects both men and women.
It usually begins during the first year of life.
Genetic
Mevalonate kinase deficiency is an autosomal recessive inherited disorder caused by the presence of 2 pathogenic mutations in the MVK gene. This gene codes for an enzyme called mevalonate kinase, involved in the synthesis of cholesterol.
Clinical
Symptoms of mevalonate kinase deficiency begin very early in life: in the first year of life, with digestive symptoms at the forefront.
Patients may present with attacks lasting 3 to 7 days on average and occurring every 1 to 2 months.
They are characterised by fever and abdominal pain in the foreground, usually associated with mouth ulcers, cervical lymph nodes and hepatomegaly (a large liver) and/or splenomegaly (a large spleen).
Between attacks, the patient has few or no symptoms, but may have residual inflammation in the blood.
Stress, fatigue, infection, trauma or, more traditionally, vaccination can all contribute to the onset of an attack. Booster vaccinations can cause painful and inflammatory local reactions.
Other symptoms may be associated: headaches, joint pain, skin rashes (very varied) and psychiatric disorders: fatigue, depression, anxiety.
Diagnostic
The diagnosis is genetic, looking for two mutations in the MVK gene. Nowadays, genetic analysis using next-generation sequencing (NGS) is recommended.
Blood tests show an inflammatory syndrome, with elevated C-reactive protein (CRP) during a crisis.
In the urine, there may be an increase in mevalonic acid during febrile attacks.
Serum Immunoglobulin D is no longer recommended as it is non-specific and insensitive.
Evolution
One complication in particular that needs to be monitored is the development of renal amyloidosis (RA), which is fortunately rare. It is recommended that blood counts, CRP and renal function be monitored every 6 months, particularly outside the crisis period.
Treatment
The aims of the treatment are to:
- Stop the symptoms.
- Prevent the onset of attacks.
- Normalise CRP between attacks.
Treatment must be recommended by an expert centre and take account of the specific nature of each case, depending on age, impact and any complications of the disease.
​
Biotherapies inhibiting interleukin-1 have proved effective in this disease. Canakinumab has marketing authorisation in France.
Anti-interleukin 6 biotherapy can be used as a second-line treatment.