It is known that monocytes and macrophages in affected individuals also produce higher levels of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) other than IL-Iβ During febrile (fever) attacks, C-reactive protein (CRP) also increases. CRP is released by liver which causes inflammation. Hyper-IgD syndrome
Hyperimmunoglobulinemia D with recurrent fever is a periodic fever syndrome originally described in 1984 by the internist Jos van der Meer, then at Leiden University Medical Centre. No more than 300 cases have been described worldwide. It is now recognised as an allelic variant of MKD. Signs and symptoms
HIDS is one of a number of periodic fever syndromes. It is characterised by attacks of fever, arthralgia, skin lesions including cyclical mouth ulcers, and diarrhea. Laboratory features include an acute phase response (elevated CRP and ESR) and markedly elevated IgD (and often IgA), although cases with normal IgD have been described.It has mainly been described in the Netherlands and France, although the international registry includes a number of cases from other countries.The differential diagnosis includes fever of unknown origin, familial Mediterranean fever (FMF) and familial Hibernian fever (or TNFα reception associated periodic syndrome/TRAPS). Cause
Virtually all people with the syndrome have mutations in the gene for mevalonate kinase, which is part of the HMG-CoA reductase pathway, an important cellular metabolic pathway. Indeed, similar fever attacks (but normal IgD) have been described in patients with mevalonic aciduria – an inborn error of metabolism now seen as a severe form of HIDS.
Both males and females are affected. The disorder has been associated with the older age of parents at the time of conception. A PRKAR1A mutation has been identified in acrodysostosis with hormone resistance. Diagnosis
Treatment
There are currently no approved treatments or standardised treatment guidelines for acrodysostosis. Management of acrodysostosis typically focuses on addressing specific symptoms that occur in each individual and may include surgery, physical therapy and special education. Research
A number of transgenic mouse models have been generated that harbour genetic mutations within genes linked to the condition in humans. These mouse models exhibit phenotypes similar to that observed in Acrodysostosis in humans. Media
The actress Olivia Colman partnered with the charity Acrodysostosis Support and Research to raise awareness for the disease. She participated in a promotional video campaign in December 2020. References
External links
"Acrodysostosis: Support and Research". "Acrodysostosis: Disease Information from NORD". National Organization for Rare Disorders. Acrodysostosis at NIHs Office of Rare Diseases