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Hyperimmunoglobulin D syndrome: Clinical manifestations and diagnosis

Yoram C Padeh, MD
Arye Rubinstein, MD
Section Editors
Jordan S Orange, MD, PhD
Robert Sundel, MD
Deputy Editor
Elizabeth TePas, MD, MS


Hyperimmunoglobulin D syndrome (HIDS, MIM #260920) is a rare, autosomal recessive genetic disorder characterized by recurrent febrile episodes typically associated with lymphadenopathy, abdominal pain, and an elevated serum polyclonal immunoglobulin D (IgD) level. Classic HIDS is due to compound heterozygous or homozygous mutation in the mevalonate kinase (MVK) gene. The underlying genetic defect is not known in variant HIDS.

Recurrent fever that is not due to infection is a clinical feature of several disorders that are collectively referred to as autoinflammatory diseases. HIDS is one of the major periodic fever syndromes, which is a subset of autoinflammatory diseases. An overview of periodic and recurrent fevers and other autoinflammatory diseases is presented separately. (See "Periodic fever syndromes and other autoinflammatory diseases: An overview".)

The clinical manifestations, laboratory features, and diagnosis of HIDS are reviewed here. Pathophysiology and management of HIDS are presented separately. (See "Hyperimmunoglobulin D syndrome: Pathophysiology" and "Hyperimmunoglobulin D syndrome: Management".)


HIDS typically presents during the first year of life [1]. The median age of onset of symptoms was six months in one series (range one week to 10 years of age) [2]. Most patients experienced their first attack within the first year of life (78.1 percent).

HIDS is equally common in males and females. More than 60 percent of patients are of Dutch or French ancestry, although HIDS cases have been reported around the world, including in the United Kingdom, Germany, Italy, Turkey, the Czech Republic, the United States, Japan, and the Arabian peninsula [1,3-6]. An internet-based registry has been created to catalog and follow known patients with HIDS.

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Literature review current through: Nov 2017. | This topic last updated: Jun 28, 2016.
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