Prevalence of Hyper IgD Syndrome
Hyper IgD syndrome (HIDS) is an extremely rare autoinflammatory disorder, with approximately 60 cases documented in the medical literature as of the mid-1990s, predominantly affecting European populations. 1, 2, 3
Epidemiological Data
The available evidence indicates HIDS is one of the rarest autoinflammatory conditions:
- A 1995 international registry identified only 60 confirmed cases worldwide, with 59 from Europe and 1 from Japan 2
- Geographic distribution shows clustering in specific European countries: The Netherlands (28 cases; 56%), France (14 cases; 20-23%), and Italy (3 cases; 6%) 1, 2, 3
- The disorder demonstrates autosomal recessive inheritance, with 18 patients from 8 families showing familial clustering, suggesting a hereditary component in approximately 40% of cases 2, 3
Context Within Primary Immunodeficiencies
To understand HIDS rarity, it's helpful to contextualize it within the broader spectrum of primary immunodeficiency disorders (PIDDs):
- Autoinflammatory disorders as a category represent less than 1% of all PIDDs 4
- The overall prevalence of symptomatic PIDDs ranges from 1 in 10,000 to 1 in 12,000 in the general population 4
- For comparison, chronic granulomatous disease (CGD) occurs in 1 in 200,000 live births, and HIDS appears even rarer than this 4
Clinical Recognition Challenges
The true prevalence may be underestimated due to several factors:
- Very early age of onset (median 0.5 years, ranging from first weeks of life to 53 years) makes diagnosis challenging 2, 3
- Serum IgD levels are typically normal until 3 years of age, delaying diagnostic confirmation in young children 5
- The disorder requires specialized testing and awareness, as it must be distinguished from other periodic fever syndromes like familial Mediterranean fever, CINCA syndrome, and FAPA syndrome 1
Important Diagnostic Considerations
Genetic testing for MVK gene mutations confirms the diagnosis, as HIDS results from bi-allelic loss-of-function variants in the mevalonate kinase gene 6
The rarity of this condition means:
- Most general practitioners and even many immunologists may never encounter a case in their career
- Referral to tertiary care centers with experience in autoinflammatory disorders is essential 6
- International registries and study groups remain critical for understanding disease prevalence and natural history 1, 3