HyperIgD

Hyper-IgD syndrome, also known as Hyper-IgD syndrome (HIDS), is a rare autoinflammatory disorder caused by biallelic mutations in the MVK gene, which encodes mevalonate kinase. Deficiency of this enzyme affects the mevalonate pathway and leads to dysregulated inflammatory responses. The condition is considered part of MVK-related disorders and is characterized by recurrent febrile episodes often accompanied by systemic symptoms. Serum IgD levels are typically elevated during attacks and may be persistently high in some individuals, but elevated IgD alone is not diagnostic.

Clinically, HIDS usually presents in infancy or early childhood with periodic fevers lasting several days, sometimes accompanied by lymphadenopathy, abdominal pain, diarrhea, pharyngitis, rash, and irritability. Attacks can be triggered by infections or stress, and the frequency and severity vary among patients. Inflammatory markers such as C-reactive protein and erythrocyte sedimentation rate are often elevated during flares.

Genetically, HIDS is inherited in an autosomal recessive pattern. MVK mutations reduce enzyme activity, leading to an imbalance in isoprenoid biosynthesis and increased production of inflammatory mediators, notably interleukin-1 (IL-1).

Diagnosis involves clinical evaluation, elevated IgD during attacks, and confirmation by MVK gene sequencing. Additional laboratory assessment may include inflammatory markers and exclusion of other periodic fever syndromes.

Management focuses on controlling symptoms and reducing attack frequency. Treatments include NSAIDs or acetaminophen for fever, steroids for severe flares, and IL-1 blockers such as anakinra or canakinumab, which have shown efficacy in many patients. Prognosis varies with attack burden and response to therapy.