Hyper IgD syndrome: Description, Causes and Risk Factors:
Alternative Name: Hyperimmunoglobulinemia D and periodic fever, Dutch-type periodic fever.
Hyper IgD syndrome is a genetic disease. It is an inborn error of the body's chemistry. Patients suffer from recurrent bouts of fever, accompanied by a variety of symptoms. These include painful swelling of lymph nodes (especially in the neck), skin rash, headache, sore throat, ulcers in the mouth, abdominal pain, vomiting, diarrhea, joint pain and joint swelling. Severely affected individuals can develop life threatening fever attacks in infancy, developmental delay, impaired vision and kidney damage. In many affected individuals, a blood component, immunoglobulin D (IgD), is elevated, giving rise to the alternative name of “hyper IgD periodic fever syndrome”.
The disease affects people of all ethnic groups, but is relatively common among the Dutch. The frequency of the disease, even in The Netherlands, is very low. Fever attacks start before the age of six years in the vast majority of patients, usually in infancy. The disease affects both boys and girls equally.
This is caused by mutations in the gene coding mevalonate kinase, an enzyme important for cholesterol synthesis. Reduction in the synthesis of anti-inflammatory isoprenylated proteins may account for the clinical syndrome.
Gene Locus: 12q24.
This results in accumulation of mevalonic acid, which will appear in the urine. Clinically, the result is recurrent fever. The worse the damage to the MVK-gene, the more severe the disease tends to be. Although the cause is genetic, fever attacks can sometimes be provoked by vaccinations, viral infections, injury or emotional stress.
The disease is inherited as an autosomal recessive disease. This means that to have hyper IgD syndrome one needs two mutated genes, one from the mother and the other from the father. So both parents are carriers (a carrier has only one mutated copy, but not the disease) rather than patients. For such a couple, the risk of having another son or daughter with hyper IgD syndrome is 1:4.
The inflammatory mechanism of this metabolic disease remains to be discovered.
The main symptom is fever, often starting with shaking chills. Fever lasts about 3-6 days and recurs at irregular intervals (weeks to months). The bouts of fever are accompanied by a variety of symptoms. These may include painful swelling of lymph nodes (especially in the neck), skin rash, headache
, sore throat
, ulcers in the mouth, abdominal pain, vomiting, diarrhea, joint pain and joint swelling. Severely affected individuals can develop life-threatening fever attacks in infancy, developmental delay, impaired vision and kidney damage.
The differential diagnosis includes fever of unknown origin, familial Mediterranean fever (FMF) and familial Hibernian fever (or TNF-reception associated periodic syndrome/TRAPS).
The diagnosis can be made chemical studies or by genetic analysis.Chemically, the abnormally high mevalonic acid can be detected in urine. Specialized laboratories can also measure the activity of the mevalonate kinase enzyme in blood or skin cells.
Genetic analysis is performed on DNA from the patient, in which the damage to the MVK genes (mutations) can be identified and measurement of serum IgD concentration.
Blood tests: The laboratory tests, as mentioned before, are important in diagnosing hyper IgD syndrome. Tests like erythrocyte sedimentation rate (ESR), CRP, serum Amyloid-A-protein (SAA), whole blood count and fibrinogen are ordered during an attack to see the extent of inflammation. These are repeated after the child becomes symptom-free, to observe if the results are back to normal, or near normal.
Cysteinyl leukotrienes (LTC4, LTD4, and LTE4): - Increased.
Urine test: A sample of urine is also tested for the presence of protein and red blood cells. There may be temporary changes during attacks. Patients with amyloidosis will have persistent levels of protein in urine tests.
There are no proven treatments to prevent attacks. Patients can expect to have recurrent bouts of fever throughout their life, although episodes tend to become less frequent after adolescence. To control the symptoms of fever and pain many patients may benefit from use of non-specific drugs like paracetamol.
In limited clinic trial to test the hypothesis that inhibition of HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase would ameliorate the inflammatory attacks, simvastatin has been tested with some success in patients with hyper-IgD syndrome. TNF inhibitors seem also to be efficient against inflammatory features.
Other medications related with hyper IgD syndrome may include anakinra, coenzyme Q10, and etanercept.
NOTE: The above information is educational purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.
DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.