AB0781 ONE, NONE, MANY: REFLECTIONS ON A RARE CASE
| Autor: | C. Galluzzo, Gilda Sandri, L. Belletti, S. Bruni, M. Cavedoni, Maria Teresa Mascia |
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| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Annals of the Rheumatic Diseases. 80:1416.2-1416 |
| ISSN: | 1468-2060 0003-4967 |
| Popis: | Background:Rare diseases are all those diseases that present, in the European Union, a prevalence of less than 5 cases per 10,000 people. The number of rare diseases is estimated at roughly 7,000 but there are also longstanding medical conditions that elude diagnosis and could be identified as rare.Objectives:Demonstrate the importance of international research in orphan diseases.Methods:We report a case of 44 y/o female patient who arrived to our observation in 2006. Short stature, early puberty, ligament laxity, BMI Results:In September 2009, the patients had been investigated at the NIH (Washington D.C.) during the “Undiagnosed Diseases Program” but without results until 2013 when the patients were informed of the detection of an ATP6V1H gene mutation never described before in humans. The gene encodes a vacuolar ATPase, a multimeric enzyme that plays several roles: is involved in endocytosis, intracellular trafficking, and protein degradation and energy production, appears to be a risk factor in the development of dyslipidemias and type II diabetes, has a bone resorption function. Also in the patient’s father were founded the same mutation and asymptomatic bone lesions. In 2016 and 2017 studies have reported mouse models of osteoporosis that were generated by knocking out the ATP6V1H gene.Conclusion:from this case it is possible to understand the difficulty of diagnosing a rare disease, the need of an international collaboration in research. From these studies it can be deduced moreover that the ATP6V1H gene could be an important target for therapeutic interventions aimed at preventing bone resorption and treating osteoporosis; evidence to support exploration of MMP9 and MMP13 as therapeutic targets for patients with ATP6V1H deficiency.This mutation seems to affect only one family, but it is possible that the penetrance of the disease-causing mutation is variable. In literature is reported an enhanced expression of MMP-9 in a variety of autoimmune diseases and neurological pathologies (2) therefore the mutation can be at the basis of other much more common pathologies.References:[1]Zhang Y, Huang H, Zhao G, Yokoyama T, Vega H, Huang Y, Sood R, Bishop K, Maduro V, Accardi J, Toro C, Boerkoel CF, Lyons K, Gahl WA, Duan X, Malicdan MC, Lin S. ATP6V1H Deficiency Impairs Bone Development through Activation of MMP9 and MMP13. PLoS Genet. 2017 Feb 3;13(2):e1006481. doi: 10.1371/journal.pgen.1006481.[2]Ram M, Sherer Y, Shoenfeld Y. Matrix metalloproteinase-9 and autoimmune diseases. J Clin Immunol. 2006 Jul;26(4):299-307. doi: 10.1007/s10875-006-9022-6.Disclosure of Interests:Gilda Sandri: None declared, Lorenza Belletti: None declared, Michele Cavedoni: None declared, Claudio Galluzzo: None declared, stefano bruni Consultant of: Genzyme, Employee of: Genzyme, Maria Teresa Mascia: None declared |
| Databáze: | OpenAIRE |
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