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Ctenidium28 (会話 | 投稿記録) en:Urbach–Wiethe disease 2024年3月8日 (金) 01:40 UTC より翻訳準備 タグ: 曖昧さ回避ページへのリンク |
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{{Infobox medical condition (new)
| name = Urbach-Wiethe disease
| synonyms = '''Lipoid proteinosis''' and '''Hyalinosis cutis et mucosae'''
| image = 3767 dp sl 2.png
| caption = Urbach–Wiethe disease in skin biopsy with [[H&E stain]].
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[[File:Autosomal recessive - en.svg|thumb|Urbach–Wiethe disease is inherited in an autosomal recessive manner.]]
'''ウルバッハ・ビーテ病''' is a very rare recessive genetic disorder, with approximately 400 reported cases since its discovery.<ref>{{cite news| url = https://www.washingtonpost.com/news/speaking-of-science/wp/2015/01/20/meet-the-woman-who-cant-feel-fear/?tid=hpModule_9d3add6c-8a79-11e2-98d9-3012c1cd8d1e&hpid=z11| title = Meet the woman who can't feel fear - The Washington Post| newspaper = [[The Washington Post]]}}</ref><ref name=DiGiandomenico-etal-2006>{{cite journal |author1=DiGiandomenico S. |author2=Masi R. |author3=Cassandrini D. |author4=El-Hachem M. |author5=DeVito R. |author6=Bruno C. |author7=Santorelli F.M. | year = 2006 | title = Lipoid proteinosis: case report and review of the literature | journal = Acta Otorhinolaryngol Ital | volume = 26 | issue = 3 | pages = 162–7 | pmid = 17063986 | pmc = 2639960 }}</ref><ref name="Andrews">{{cite book |author1=James, William D. |author2=Berger, Timothy G. |title=Andrews' Diseases of the Skin: clinical Dermatology |publisher=Saunders Elsevier |year=2006 |isbn=978-0-7216-2921-6 |display-authors=etal}}</ref> It was first officially reported in 1929 by [[Erich Urbach]] and [[Camillo Wiethe]],<ref>{{WhoNamedIt|synd|924}}</ref><ref>{{cite journal | author = Urbach E, Wiethe C | year = 1929 | title = Lipoidosis cutis et mucosae | journal = Virchows Archiv für pathologische Anatomie und Physiologie und für klinische Medizin | volume = 273 | issue = 2 | pages = 285–319 | doi = 10.1007/bf02158983 | s2cid = 42016927 | doi-access = free }}</ref> although cases may be recognized dating back as early as 1908.<ref name=Caro-1978>{{cite journal | author = Caro I | year = 1978 | title = Lipoid proteinosis | journal = International Journal of Dermatology | volume = 17 | issue = 5 | pages = 388–93 | doi = 10.1111/ijd.1978.17.5.388 | pmid = 77850 | s2cid = 43544386 }}</ref><ref name="isbn0-7817-3742-7">{{cite book |author1=Lever, Walter F. |author2=Elder, David A. |title=Lever's histopathology of the skin |publisher=[[Lippincott Williams & Wilkins]] |___location=Hagerstwon, MD |year=2005 |pages=440 |isbn=978-0-7817-3742-5 }}</ref><ref>{{cite journal | author =Siebenmann F. | year = 1908 | title = Über Mitbeteilingung der Schleimhaut bei allgemeiner Hyperkeratose der Haut | journal = Arch Laryngol | volume = 20 | pages = 101–109 }}</ref>
The symptoms of the disease vary greatly from individual to individual. They may include a hoarse voice, [[lesion]]s and scarring on the skin, easily damaged skin with poor wound healing, dry, wrinkly skin, and beading of the [[papule]]s around the eyelids.<ref name=Caro-1978/><ref name=Hamada-2002-C&ED>{{Cite journal | last1 = Hamada | first1 = T. | title = Lipoid proteinosis | journal = Clinical and Experimental Dermatology | volume = 27 | issue = 8 | pages = 624–629 | year = 2002 | doi = 10.1046/j.1365-2230.2002.01143.x| pmid = 12472532 | s2cid = 28344373 }}</ref><ref name=Appenzeller-etal-2006-Neuroimaging16/> All of these are results of a general thickening of the skin and [[mucous membrane]]s. In some cases there is also a hardening of brain tissue in the [[medial temporal lobe]]s, which can lead to [[epilepsy]] and neuropsychiatric abnormalities.<ref name = Staut-1998>{{Cite journal | last1 = Staut | first1 = C. C. V. | last2 = Naidich | first2 = T. P. | title = Urbach-Wiethe Disease(Lipoid Proteinosis) | journal = Pediatric Neurosurgery | volume = 28 | issue = 4 | pages = 212–214 | year = 1998 | pmid = 9732251 | doi = 10.1159/000028653| s2cid = 46862405 }}</ref> The disease is typically not life-threatening and patients do not show a decreased [[life expectancy|life span]].<ref name=Appenzeller-etal-2006-Neuroimaging16>{{Cite journal | title = Amygdalae Calcifications Associated with Disease Duration in Lipoid Proteinosis | journal = Journal of Neuroimaging | volume = 16 | issue = 2 | pages = 154–156 | year = 2006 | pmid = 16629738 | doi = 10.1111/j.1552-6569.2006.00018.x| last1 = Appenzeller | first1 = S | last2 = Chaloult | first2 = E | last3 = Velho | first3 = P | last4 = De Souza | first4 = E. M. | last5 = Araújo | first5 = V. Z. | last6 = Cendes | first6 = F | last7 = Li | first7 = L. M. | s2cid = 30567332 }}</ref>
Because Urbach–Wiethe disease is an [[autosomal recessive]] condition individuals can be [[genetic carrier|carriers]] of the disease but show no symptoms. The disease is caused by loss-of-function [[mutation]]s to [[chromosome 1]] at 1q21, the extracellular matrix protein 1 ([[ECM1]]) gene.<ref name = Hamada-etal-2002>{{cite journal |author1=Hamada T. |author2=McLean WHI |author3=Ramsay M. |author4=Ashton GHS |author5=Nanda A. | display-authors = etal | year = 2002 | title = Lipoid proteinosis maps to 1q21 and is caused by mutations in the extracellular matrix protein 1 gene (ECM1) | journal = Human Molecular Genetics | volume = 11 | issue = 7| pages = 833–40 | pmid = 11929856 | doi = 10.1093/hmg/11.7.833 | doi-access = }}</ref> The dermatological symptoms are caused by a buildup of a [[hyaline]] material in the dermis and the thickening of the [[basement membrane]]s in the skin.<ref name=Hamada-2002-C&ED/> Urbach–Wiethe disease is typically diagnosed by its clinical dermatological manifestations, particularly the beaded papules on the eyelids. The discovery of the mutations within the ECM1 gene has allowed the use of [[genetic testing]] to confirm an initial clinical [[diagnosis]]. [[Periodic acid-Schiff]] (PAS) and [[immunohistochemistry|immunohistochemical]] staining may also be used for diagnosis.<ref name=Caro-1978/><ref name = Chan-etal-2007>{{cite journal |author1=Chan I. |author2=Liu L. |author3=Hamada T. |author4=Sethuraman G. |author5=McGrath J.A. | year = 2007 | title = The molecular basis of lipoid proteinosis: mutations in extracellular matrix protein 1 | journal = Experimental Dermatology | volume = 16 | issue = 11 | pages = 881–90 | doi = 10.1111/j.1600-0625.2007.00608.x | pmid = 17927570 | doi-access = free }}</ref>
Currently, there is no cure for Urbach–Wiethe disease although there are ways to individually treat many of its symptoms.<ref name=DiGiandomenico-etal-2006/> The discovery of the mutations of the ECM1 gene has opened the possibility of gene therapy or a recombinant ECM1 protein for Urbach–Wiethe disease treatment, but neither of these options are currently available. Some researchers are examining patients with Urbach–Wiethe disease to learn more about other conditions that exhibit similar neurological symptoms, such as [[autism]].
== Symptoms and signs ==
Urbach–Wiethe disease is characterized by both [[neurological]] and dermatological symptoms.<ref name = Siebert-etal-2003>{{cite journal |author1=Siebert M. |author2=Markowitsch H.J. |author3=Bartel P. | year = 2003 | title = Amygdala, affect and cognition: evidence from 10 patients with Urbach-Wiethe disease | journal = Brain | volume = 126 | issue = 12 | pages = 2627–37 | doi = 10.1093/brain/awg271 | pmid = 12937075 | doi-access = free }}</ref><ref>{{cite journal |author1=Mallory S.B. |author2=Krafchick B.R. |author3=Holme S.A. |author4=Lenane P. |author5=Krafchik B.R. | year = 2005 | title = What syndrome is this? Urbach-Weithe syndrome (lipoid proteinosis) | journal = Pediatric Dermatology | volume = 22 | issue = 3 | pages = 266–7 | doi = 10.1111/j.1525-1470.2005.22321.x | pmid = 15916581 | s2cid = 44925736 }}</ref>
=== Dermatological ===
Although [[symptom]]s can vary greatly between affected individuals, even those within the same family, symptoms normally begin in [[infancy]] and are typically a result of thickening skin and mucous membranes.<ref name=DiGiandomenico-etal-2006/> The first symptom is often a weak cry or a hoarse voice due to a thickening of the vocal cords. The [[hoarse]] voice can be one of the most striking clinical manifestations of the disease.<ref name=Hamada-2002-C&ED/> Lesions and scars also appear on the [[skin]], usually the [[face]] and the [[Anatomical terms of ___location#Proximal and distal|distal]] parts of the limbs.<ref name=Caro-1978/> This is often the result of poor wound healing and the scarring continues to increase as the patient ages, leaving the skin with a waxy appearance. Skin may be easily damaged as a result of only a minor trauma or injury, leaving many blisters and additional scars.<ref name=Appenzeller-etal-2006-Neuroimaging16/> The skin is also usually very dry and wrinkly. White or yellow [[Infiltration (medical)|infiltrates]] form on the lips, [[buccal mucosa]], [[tonsils]], [[uvula]], [[epiglottis]] and [[frenulum]] of the tongue.<ref name=Caro-1978/> This can lead to [[upper respiratory tract infection]] and sometimes requires [[tracheostomy]] to relieve the symptom.<ref name=Hamada-2002-C&ED/> Too much thickening of the frenulum can restrict tongue movement and may result in [[speech impediment]]s.<ref name=Thornton-etal-2008>{{cite journal |author1=Thornton H.B. |author2=Nel D. |author3=Thornton D. |author4=van Honk J. |author5=Baker G.A. |author6=Stein D.J. | year = 2008 | title = The neuropsychiatry and neuropsychology of lipoid proteinosis | journal = Journal of Neuropsychiatry and Clinical Neurosciences | volume = 20 | issue = 1 | pages = 86–92 | doi = 10.1176/jnp.2008.20.1.86 | pmid = 18305289 | doi-access = free }}</ref> Beading of the papules around the [[eyelid]]s is a very common symptom and is often used as part of a [[diagnosis]] of the [[disease]]. Some other [[dermatological]] symptoms that are sometimes seen but less common include [[hair loss]], [[parotitis]] and other [[Dentistry|dental]] abnormalities, [[corneal]] ulceration, and focal degeneration of the [[macula]].<ref name=Bahadir-etal-2006>{{cite journal |author1=Bahadir S. |author2=Cobanoglu U. |author3=Kapicioglu Z. |author4=Kandil S.T. |author5=Cimsit G. | display-authors = etal | year = 2006 | title = Lipoid proteinosis: A case with ophthalmological and psychiatric findings | journal = The Journal of Dermatology | volume = 33 | issue = 3 | pages = 215–8 | doi = 10.1111/j.1346-8138.2006.00049.x | pmid = 16620230 | s2cid = 34699559 }}</ref>
=== Neurological ===
Although the dermatological changes are the most obvious symptoms of Urbach–Wiethe disease, many patients also have neurological symptoms. About 50–75% of the diagnosed cases of Urbach–Wiethe disease also show bilateral symmetrical [[calcification]]s on the medial [[temporal lobe]]s.<ref>{{cite journal |author1=Hurlemann R. |author2=Wagner M. |author3=Hawellek B. |author4=Reich H. |author5=Pieperhoff P. |author6=Amunts K. | display-authors = etal | year = 2007 | title = Amygdala control of emotion-induced forgetting and remembering: Evidence from Urbach-Wiethe disease | journal = Neuropsychologia | volume = 45 | issue = 5 | pages = 877–84 | doi = 10.1016/j.neuropsychologia.2006.08.027 | pmid = 17027866 | hdl = 21.11116/0000-0001-B8EF-3 | s2cid = 4101263 | hdl-access = free }}</ref> These calcifications often affect the [[amygdala]] and the periamygdaloid [[gyrus|gyri]].<ref name = Staut-1998/> The amygdala is thought to be involved in processing biologically relevant stimuli and in emotional long-term memory, particularly those associated with [[fear]], and both [[Positron emission tomography|PET]] and [[Magnetic resonance imaging|MRI]] scans have shown a correlation between amygdala activation and episodic memory for strongly emotional stimuli.<ref name=Siebert-etal-2003/> Therefore, Urbach–Wiethe disease patients with calcifications and [[lesions]] in these regions may suffer impairments in these systems. These calcifications are the result of a buildup of [[calcium]] deposits in the [[blood vessel]]s within this brain region. Over time, these vessels [[Atherosclerosis|harden]] and the tissue they are a part of dies, causing lesions. The amount of calcification is often related to disease duration.<ref name=Appenzeller-etal-2006-Neuroimaging16/> The true prevalence of these calcifications is difficult to accurately state as not all patients undergo [[neuroimaging|brain imaging]]. Some patients also exhibit [[epilepsy]] and neuropsychiatric abnormalities. Epilepsy symptoms could begin with light anxiety attacks and can be controlled with anti-epileptic medications.<ref name=Appenzeller-etal-2006-Neuroimaging16/> Other patients present with symptoms similar to schizophrenia while some suffer from mood, [[anxiety]], and psychotic disorders.<ref name = Thornton-etal-2008/><ref name = Cinaz-1993>{{cite journal |author1=Cinaz P. |author2=Guvenir T. |author3=Gonlusen G. | year = 1993 | title = Lipoid proteinosis: Urbach-Wiethe disease | journal = Acta Paediatrica | volume = 82 | issue = 11 | pages = 892–3 | doi = 10.1111/j.1651-2227.1993.tb12590.x | pmid = 8241657 | s2cid = 31104438 }}</ref> [[File:Chromosome 1.svg|frame|Chromosome 1, where the ECM1 mutation occurs at 1[[Centromere#Position|q]]21]]
== Causes ==
Researchers have mapped Urbach–Wiethe disease to [[chromosome 1]] at 1q21 and specifically identified the extracellular matrix protein 1 ([[ECM1]]) gene as the gene containing mutations that can lead to the development of the condition.<ref name = Hamada-etal-2002/> At this point, 41 different mutations within ECM1 have been reported to lead to Urbach–Wiethe disease.<ref name = Chan-etal-2007/> These were all [[zygosity|homozygous]] loss-of-function mutations (i.e. [[Nonsense mutation|nonsense]], [[Frameshift mutation|frameshift]] or internal [[Deletion mutation|deletions]]).<ref name=Hamada-2002-C&ED/> It is an [[autosomal recessive]] condition,<ref name=DiGiandomenico-etal-2006/><ref name=Chan-etal-2007/> requiring two mutated copies of the ECM1 gene to cause the disease.<ref>{{cite journal |vauthors = Morovvati S, Farshadyeganeh P, Hamidizadeh M, Morovvati Z, Mohammadi SD|date=August 2018 |title = Mutation Analysis of ECM1 Gene in Two Related Iranian Patients Affected by Lipoid Proteinosis|url= https://www.researchgate.net/publication/327250566|journal= Acta Medica Iranica |volume=56 |issue=7 |pages=474–477 |access-date= 1 September 2020}}</ref>
ECM1 codes for a [[glycoprotein]] of previously unknown origin. The discovery that the loss of ECM1 expression leads to the symptoms associated with Urbach–Wiethe disease suggests that ECM1 may contribute to skin adhesion, epidermal differentiation, and wound healing and scarring.<ref name=Hamada-etal-2002/> It is also thought to play a role in endochondral bone formation, tumor biology, endothelial cell proliferation and blood vessel formation.<ref name=Hamada-2002-C&ED/>
The dermatological symptoms are caused by a buildup of a [[hyaline]] material in the dermis and the thickening of the basement membranes in the skin.<ref name=Hamada-2002-C&ED/> The nature of this material is unknown, but researchers have suggested that it may be a glycoprotein, a [[glycolipid]], an acid [[mucopolysaccharide]], altered [[collagen]] or elastic tissue.<ref name=Caro-1978/>
== Diagnosis ==
Urbach–Wiethe disease is typically diagnosed by its clinical dermatological manifestations, particularly the beaded papules on the eyelids. Doctors can also test the hyaline material with a periodic acid-Schiff (PAS) staining, as the material colors strongly for this stain.<ref name=Caro-1978/>
Immunohistochemical skin labeling for [[antibody|antibodies]] for the ECM1 protein as labeling has been shown to be reduced in the skin of those affected by Urbach–Wiethe disease.<ref name = Chan-etal-2007/> Staining with anti-type IV collagen antibodies or anti-type VII collagen antibodies reveals bright, thick bands at the [[dermoepidermal junction]].<ref name=Hamada-2002-C&ED/>
Non-contrast [[computed tomography|CT scans]] can image calcifications, but this is not typically used as a means of diagnosing the disease. This is partly due to the fact that not all Urbach-Wiethe patients exhibit calcifications, but also because similar lesions can be formed from other diseases such as [[herpes simplex]] and [[encephalitis]]. The discovery of mutations within the ECM1 gene has allowed the use of genetic testing to confirm initial clinical diagnoses of Urbach–Wiethe disease. It also allows doctors to better distinguish between Urbach–Wiethe disease and other similar diseases not caused by mutations in ECM1.{{cn|date=October 2021}}
== Treatment ==
Currently, there is no cure for Urbach–Wiethe disease although there are some ways to individually treat many of its symptoms. There has been some success with oral [[dimethyl sulfoxide]] (DMSO) and intralesional [[heparin]], but this is not true in all cases.<ref name=Hamada-2002-C&ED/><ref name = Cinaz-1993/> D-[[penicillamine]] has also shown promise, but has yet to have been used extensively.<ref name = Chan-etal-2007/> There are also some reports of patients being treated with [[etretinate]], a drug typically prescribed to treat [[psoriasis]].<ref name=Bahadir-etal-2006/> In some cases, calcifications in the brain can lead to abnormal electrical activity among neurons. Some patients are given anti-seizure medication to help deal with these abnormalities. [[Tracheostomy]] is often used to relieve upper respiratory tract infections. [[Carbon dioxide]] laser surgery of thickened [[vocal folds|vocal cords]] and beaded eyelid papules have improved these symptoms for patients.<ref name=Hamada-2002-C&ED/> The discovery of the mutations of the ECM1 gene has opened the possibility of gene therapy or a [[Recombinant DNA|recombinant]] EMC1 protein for Urbach–Wiethe disease treatment, but neither of these two options are currently available.{{cn|date=October 2021}}
== Prognosis ==
Urbach–Wiethe disease is typically not a life-threatening condition.<ref name=DiGiandomenico-etal-2006/> The life expectancy of these patients is normal as long as the potential side effects of thickening mucosa, such as respiratory obstruction, are properly addressed.<ref name=Appenzeller-etal-2006-Neuroimaging16/> Although this may require a tracheostomy or carbon dioxide laser surgery, such steps can help ensure that individuals with Urbach–Wiethe disease are able to live a full life. Oral [[dimethyl sulfoxide]] (DMSO) has been shown to reduce skin lesions, helping to minimize discomfort for these individuals.<ref name=Hamada-2002-C&ED/>
== Incidence ==
Urbach–Wiethe disease is very rare; there are fewer than 300 reported cases in [[medical literature]].<ref name=DiGiandomenico-etal-2006/> Although Urbach–Wiethe disease can be found worldwide, almost a quarter of reported diagnoses are in [[South Africa]].<ref name=DiGiandomenico-etal-2006/> Many of these are in patients of [[Dutch people|Dutch]], [[German people|German]], and [[Khoisan]] ancestry.<ref name=DiGiandomenico-etal-2006/><ref name=Hamada-etal-2002/> This high frequency is thought to be due to the [[founder effect]].<ref name = Chan-etal-2007/> Due to its recessive genetic cause and the ability to be a carrier of the disease without symptoms, Urbach–Wiethe disease often runs in families. In some regions of South Africa, up to one in 12 individuals may be carriers of the disease.<ref name=Hamada-2002-C&ED/> Most of the case studies involving Urbach–Wiethe disease patients involve only one to three cases and these cases are often in the same family. Due to its low incidence, it is difficult to find a large enough number of cases to adequately study the disease.{{cn|date=October 2021}}
== History ==
In 1908, what appears to be the first case of Urbach–Wiethe disease was reported by [[Friedrich Siebenmann (otolaryngologist)|Friedrich Siebenmann]], a professor of [[otolaryngology]] in [[Basel]], [[Switzerland]]. In 1925, [[Friedrich Miescher]], a Swiss dermatologist, reported on three similar patients.<ref name=Caro-1978/> An official report of Urbach–Wiethe disease was first described in 1929 by a Viennese dermatologist and otorhinolaryngologist, Urbach and Wiethe.<ref name = Hamada-etal-2002/> Its original name of 'lipoidosis cutis et mucosae' was changed to 'lipoid proteinosis cutis et mucosae' due to Urbach's belief that the condition was due to abnormal [[lipid]] and [[protein]] deposits within the tissues.<ref name = Hamada-etal-2002/> Some have debated as to whether or not the disease is actually a form of [[mucopolysaccharidosis]], [[amyloidosis]], or even [[porphyria]]. The discovery of the Urbach–Wiethe disease causing mutation to the ECM1 gene has now provided a definitive way to differentiate Urbach–Wiethe disease from these other conditions.<ref name=Hamada-2002-C&ED/>
== See also ==
* [[Klüver–Bucy syndrome]]
* [[S.M. (patient)]]
* [[List of cutaneous conditions]]
* [[List of radiographic findings associated with cutaneous conditions]]
== References ==
{{Reflist}}
== External links ==
{{Medical resources
| DiseasesDB = 30808
| ICD10 = {{ICD10|E|78|8|e|70}}
| ICD9 = {{ICD9|272.8}}
| ICDO =
| OMIM = 247100
| MedlinePlus =
| eMedicineSubj = derm
| eMedicineTopic = 241
| MeshID = D008065
| SNOMED CT = 38692000
}}
{{Scleroprotein disease}}
{{DEFAULTSORT:うるはつはひいてひよう}}
<!--[[Category:Lipid metabolism disorders]]
[[Category:Autosomal recessive disorders]]
[[Category:Skin conditions resulting from errors in metabolism]]
[[Category:Rare diseases]]
[[Category:Diseases named for discoverer]]-->
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