The MVK gene at 12q24 codes for mevalonate kinase a 396 amino acid. Defects cause:
Hyperimmunoglobulinemia D and periodic fever syndrome (HIDS)
Hyperimmunoglobulin D syndrome (HIDS, hyperimmunoglobulinemia D and periodic fever syndrome, hyper Ig D syndrome, mevalonate kinase deficiency) is an autosomal recessive periodic syndrome, found mostly in people of Dutch or French extraction. There is a big database in Nijmegen, where genetic testing is done. Caused by MVK gene mutations on chromosome 12p with recurrent febrile attacks starting under 1yr of age. Attacks last 3-7 days, so may or may not be shorter than attacks in TRAPS, and occur every 4-8 weeks. There is some mevalonate kinase activity from 1% to about 10% of normal causing:
- High serum IgD level
- Recurrent high fever, typically every 2 months
- Neutrophil leukocytosis in absence of infection
- Skin rash
- Abdo pain, vomiting and diarrhoea (cf constipation of TRAPS)
- Headache, arthralgia
- Swollen cervical lymphadenopathy - very common, cf TRAPS
- Non-destructive arthritis
Diagnosis is by finding of high IgD (>100U/ml); most also have high IgA (with or without raised IgG and IgM), which is an important clue. Increased mevalonic acid is found in the urine during fever, but if diagnosis suspected it is easy to just go straight for genetic test. Febrile attacks in response to immunizations are often reported so may be another clue.
Attacks tend to diminish with age without completely disappearing; amyloidosis seems to occur only rarely (cf TRAPS).
- Autosomal with infantile onset.
Mevalonic aciduria (MEVA)
- Mevalonic acid accumulation because of failure of conversion to 5-phosphomevalonic acid causing: