The new hyper-IgD syndrome ( HIDS ), so named in 1995, was described in 1984 by Van der Meer et al. HIDS is probably inherited as an autosomal recessive trait. Very recently, mutations in the mevalonate kinase gene were shown to cause HIDS.. The aim of this study is to present the first HIDS patient diagnosed in Macedonia.

Case report:  Forteen years old boy, with no consanguinity in the families and no additional family members affected. The febrile attacks started at age of 2 months. Fever was accompanied by malaise, fatigue, abdominal pain and anorexia. Pharyngitis and sinusitis was documented several times, enterocolitis once, pneumonia twice, febrile seizures once. The rashes (maculopapular) were reported several times. He had recurrent swelling of the hands and feet during febrile attacks and arthritis of metacarpal and metatarsal joints. Lymphadenopathy and moderate hepato-splenomegaly were present. Growth and development were normal. Childhood vaccinations were followed by fever. Acute-phase response with granulocytosis and enhanced erythrocyte sedimentation rate was detected. We have no laboratory possibilities to detect IgD, but we detected increased level of IgA (7,53 g/l). A positive correlation of IgD with IgA and IgE was noted by others. After the exclusion of infectious and non-infectious causes of fever, we consider him as having HIDS. The molecular diagnosis was confirmed in Clinical Genetics Center Nijmegen

(The Netherlands ) were it was detected heterozygous in respectively exon 5 and exon 10 of the MVK gene by sequence analysis (T188X and V377IIe). V377IIe (G-->A) is the most common mutation.

The term auto-inflammatory disorders has been coined to describe a group of conditions characterized by spontaneously relapsing and remitting bouts of systemic inflammation without apparent involvement of antigen-specific T cells or significant production of auto-antibodies. DNA analysis has greatly enhanced the clinical characterization of these conditions. Most HIDS patients have mutations in the MVK gene, but the clinical variability observed cannot be explained by genotypic differences. Periodic fever and elevated IgD can result from other, still unknown, causes. Hence, testing for MVK deficiency is necessary in patients with unexplained periodic fever.