ROSAH syndrome is a genetic disease of innate immune activation.[1] ROSAH stands for Retinal dystrophy, Optic nerve edema, Splenomegaly, Anhidrosis and Headache and the name emphasizes some, but not all, of the features that can be associated with the syndrome.[2] The disease is inherited in an autosomal dominant manner and caused by heterozygous missense mutations in the ALPK1 gene, an innate immune sensor for bacterial sugars. [3]
ROSAH syndrome
ROSAH syndrome is inherited via an autosomal dominant manner
While the initial descriptions of ROSAH syndrome emphasized the ocular manifestations of the disease, it is now clear that ROSAH syndrome can also present with a range of systemic features including recurrent fever, uveitis, deforming arthritis, AA amyloidosis, meningeal enhancement and premature mineralisation of the basal ganglia, substantia nigra and red nuclei on MRI. [2][1] Additionally, clinical features not conventionally attributed to inflammation have also been reported and included short dental roots, enamel defects and decreased salivary flow.[1]
Pathophysiologyedit
ALPK1’s role in human physiology and immune regulation is still under investigation but the protein is known to act as a sensor for bacterial sugars.[3] ROSAH syndrome patients’ primary samples and in vitro assays with mutated ALPK1 constructs have shown immune activation with increased NF-κB signaling, STAT1 phosphorylation and interferon gene expression signature.[1]
Geneticsedit
This condition is caused by mutations in the ɑ-kinase gene (ALPK1) gene. This gene is located on the long arm of chromosome 4 (4q25). The inheritance of this condition is autosomal dominant.
Some features of the disease are amenable to immunomodulatory therapy.[1] However, additional studies will be need to determine if immunomodulation can mitigate the risk of progressive vision loss in this disease.
Epidemiologyedit
The prevalence is not known. To date, less than 50 individuals with ROSAH syndrome have been described in the medical literature. [1][2]
Historyedit
This condition was first described in 2012 prior to the discovery of the genetics and naming of the condition.[4] The genetic basis of this condition was first published in an ARVO abstract in 2013 and in a complete article in 2019.[2] In 2022, ROSAH Syndrome Foundation [1] was established to serve patients with ROSAH syndrome by providing information and connecting them to other individuals living with ROSAH syndrome.[5]
Referencesedit
^ abcdefgKozycki CT, Kodati S, Huryn L, et al. (2022). "Gain-of-function mutations in ALPK1 cause an NF-κB-mediated autoinflammatory disease: functional assessment, clinical phenotyping and disease course of patients with ROSAH syndrome". Annals of the Rheumatic Diseases. 81 (10): 1453–1464. doi:10.1136/annrheumdis-2022-222629. ISSN 0003-4967. PMC9484401. PMID 35868845.
^ abcdeWilliams LB, Javed A, Sabri A, Morgan DJ, Huff CD, Grigg JR, Heng XT, Khng AJ, Hollink IHIM, Morrison MA, Owen LA, Anderson K, Kinard K, Greenlees R, Novacic D, Nida Sen H, Zein WM, Rodgers GM, Vitale AT, Haider NB, Hillmer AM, Ng PC, Shankaracharya, Cheng A, Zheng L, Gillies MC, van Slegtenhorst M, van Hagen PM, Missotten TOAR, Farley GL, Polo M, Malatack J, Curtin J, Martin F, Arbuckle S, Alexander SI, Chircop M, Davila S, Digre KB, Jamieson RV, DeAngelis MM (2019) ALPK1 missense pathogenic variant in five families leads to ROSAH syndrome, an ocular multisystem autosomal dominant disorder. Genet Med doi: 10.1038/s41436-019-0476-3
^Tantravahi, Srinivas (March 2012). "An Inherited disorder with splenomegaly, cytopenias, and vision loss". American Journal of Medical Genetics. 158A (3): 475–481. doi:10.1002/ajmg.a.34437. PMC4242507. PMID 22307799.
rosah, syndrome, this, article, multiple, issues, please, help, improve, discuss, these, issues, talk, page, learn, when, remove, these, template, messages, this, article, includes, list, general, references, lacks, sufficient, corresponding, inline, citations. This article has multiple issues Please help improve it or discuss these issues on the talk page Learn how and when to remove these template messages This article includes a list of general references but it lacks sufficient corresponding inline citations Please help to improve this article by introducing more precise citations June 2019 Learn how and when to remove this template message This article needs additional citations for verification Please help improve this article by adding citations to reliable sources Unsourced material may be challenged and removed Find sources ROSAH syndrome news newspapers books scholar JSTOR June 2019 Learn how and when to remove this template message Learn how and when to remove this template message ROSAH syndrome is a genetic disease of innate immune activation 1 ROSAH stands for Retinal dystrophy Optic nerve edema Splenomegaly Anhidrosis and Headache and the name emphasizes some but not all of the features that can be associated with the syndrome 2 The disease is inherited in an autosomal dominant manner and caused by heterozygous missense mutations in the ALPK1 gene an innate immune sensor for bacterial sugars 3 ROSAH syndromeROSAH syndrome is inherited via an autosomal dominant mannerCausesMutation in ALPK1 gene Contents 1 Signs and symptoms 2 Pathophysiology 3 Genetics 4 Diagnosis 5 Management 6 Epidemiology 7 History 8 References 9 External linksSigns and symptoms editWhile the initial descriptions of ROSAH syndrome emphasized the ocular manifestations of the disease it is now clear that ROSAH syndrome can also present with a range of systemic features including recurrent fever uveitis deforming arthritis AA amyloidosis meningeal enhancement and premature mineralisation of the basal ganglia substantia nigra and red nuclei on MRI 2 1 Additionally clinical features not conventionally attributed to inflammation have also been reported and included short dental roots enamel defects and decreased salivary flow 1 Pathophysiology editALPK1 s role in human physiology and immune regulation is still under investigation but the protein is known to act as a sensor for bacterial sugars 3 ROSAH syndrome patients primary samples and in vitro assays with mutated ALPK1 constructs have shown immune activation with increased NF kB signaling STAT1 phosphorylation and interferon gene expression signature 1 Genetics editThis condition is caused by mutations in the ɑ kinase gene ALPK1 gene This gene is located on the long arm of chromosome 4 4q25 The inheritance of this condition is autosomal dominant Diagnosis editCurrently screening for ROSAH syndrome is initiated upon a physician s judgement Genetic testing for ROSAH syndrome can be performed as either targeted single gene testing through Sanger sequencing or a multi gene test through whole exome sequencing or whole genome sequencing 2 1 Management editSome features of the disease are amenable to immunomodulatory therapy 1 However additional studies will be need to determine if immunomodulation can mitigate the risk of progressive vision loss in this disease Epidemiology editThe prevalence is not known To date less than 50 individuals with ROSAH syndrome have been described in the medical literature 1 2 History editThis condition was first described in 2012 prior to the discovery of the genetics and naming of the condition 4 The genetic basis of this condition was first published in an ARVO abstract in 2013 and in a complete article in 2019 2 In 2022 ROSAH Syndrome Foundation 1 was established to serve patients with ROSAH syndrome by providing information and connecting them to other individuals living with ROSAH syndrome 5 References edit a b c d e f g Kozycki CT Kodati S Huryn L et al 2022 Gain of function mutations in ALPK1 cause an NF kB mediated autoinflammatory disease functional assessment clinical phenotyping and disease course of patients with ROSAH syndrome Annals of the Rheumatic Diseases 81 10 1453 1464 doi 10 1136 annrheumdis 2022 222629 ISSN 0003 4967 PMC 9484401 PMID 35868845 a b c d e Williams LB Javed A Sabri A Morgan DJ Huff CD Grigg JR Heng XT Khng AJ Hollink IHIM Morrison MA Owen LA Anderson K Kinard K Greenlees R Novacic D Nida Sen H Zein WM Rodgers GM Vitale AT Haider NB Hillmer AM Ng PC Shankaracharya Cheng A Zheng L Gillies MC van Slegtenhorst M van Hagen PM Missotten TOAR Farley GL Polo M Malatack J Curtin J Martin F Arbuckle S Alexander SI Chircop M Davila S Digre KB Jamieson RV DeAngelis MM 2019 ALPK1 missense pathogenic variant in five families leads to ROSAH syndrome an ocular multisystem autosomal dominant disorder Genet Med doi 10 1038 s41436 019 0476 3 a b Zhou Ping She Yang Dong Na Li Peng He Huabin Borio Alessio Wu Qingcui Lu Shan Ding Xiaojun Cao Yong Xu Yue Gao Wenqing Dong Mengqiu Ding Jingjin Wang Da Cheng Zamyatina Alla Shao Feng September 2018 Alpha kinase 1 is a cytosolic innate immune receptor for bacterial ADP heptose Nature 561 7721 122 126 Bibcode 2018Natur 561 122Z doi 10 1038 s41586 018 0433 3 ISSN 1476 4687 PMID 30111836 S2CID 52009376 Tantravahi Srinivas March 2012 An Inherited disorder with splenomegaly cytopenias and vision loss American Journal of Medical Genetics 158A 3 475 481 doi 10 1002 ajmg a 34437 PMC 4242507 PMID 22307799 ROSAH Syndrome Foundation rosahsyndrome org External links edit Retrieved from https en wikipedia org w index php title ROSAH syndrome amp oldid 1182161877, wikipedia, wiki, book, books, library,
