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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'''(ウルバッハ・ビーテびょう、[[英語|英]]: Urbach–Wiethe diseases)は非常に稀な[[潜性]][[遺伝疾患]]で、症例はこの疾患が初めて報告されてから現在に至るまでおよそ400件程度である<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>。19291908年にオーストリアの[[:en:Erich_Urbach|エーリヒ・ウルバッハ]]と[[:en:Camillo_Wiethe|カミーロ・ビーテ]]によっ初めて正式に報告されたが<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>、実際の症例が確認されているのは1908年のことである<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>、1929年に[[オーストリア]]のエーリヒ・ウルバッハとカミーロ・ビーテによって正式に報告された。<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>
症状は個人差が大きく、声のかすれ、病斑や瘢痕、easily damaged skin with poor wound healing皮膚の[[自然治癒力]]の低下、肌の乾燥やしわ、瞼周辺の[[丘疹]]などが確認されている<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/>。これらは肌や粘膜の肥厚によって引き起こされる。他にも[[側頭葉]]の脳組織の硬化によってり[[てんかん]]や精神神経系の異常をきたす場合もある<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>。一般的には、命に関わったり、余命が短くなるようなことはないとされている<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>。
ウルバッハ・ビーテ病は常染色体潜性であるため、疾患の保因者であっても症状が現れないことがある。この病気は[[1番染色体 (ヒト)|1番染色体]]の1q21に位置する[[細胞外マトリックス]]タンパク質1(ECM1)遺伝子の機能喪失型[[突然変異]]に起因する機能不全によって引き起こされる<ref name="Hamada-etal-2002">{{cite journal|author1=Hamada T.|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|doi=10.1093/hmg/11.7.833|pmid=11929856|author2=McLean WHI|author3=Ramsay M.|author4=Ashton GHS|author5=Nanda A.|display-authors=|doi-access=}}</ref>。皮膚に関する症状は主に[[真皮]]における{{仮リンク|ヒアリン|en|Hyaline}}の分泌や皮膚の基底膜がの肥厚するが要因となる<ref name="Hamada-2002-C&ED" />。ウルバッハ・ビーテ病診断は特に瞼周辺の丘疹といった臨床症状により診断ってなされる。ECM1遺伝子における内の突然変異が確認発見された場合はことで、最初の臨床診断を[[遺伝子診断]]によりconfirm an initial diagnosisことがあで確認できるようになった。また、PAS染色や[[免疫組織化学染色]](IHC)も診断に使用されることがある<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>。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. 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. 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.
現在この疾患に対する根本的な治療法は確立されていないが、各々の症状を対処することは可能である<ref name=DiGiandomenico-etal-2006/>。原因がECM1遺伝子内の突然変異だと判明したことで、遺伝子治療やECM1遺伝子の再結合などの可能性が拓けてきたが、どちらも実現には至っていない。
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]].
== 症状と兆候 ==
Urbach–Wiethe disease is characterized by both ウルバッハ・ビーテ病はおおまかに[[neurological神経系]] and dermatological symptoms.と皮膚に関する症状に分類される<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>。
=== 皮膚 ===
症状は罹患者によって、また同じ家族内であっても大きく異なるが、一般的に症状は乳幼児期に始まり、皮膚や粘膜の肥厚などが挙げられる<ref name="DiGiandomenico-etal-2006" />。初期の症状は声帯の肥厚によるかすれ声であることが多く、これはこの疾患において最も顕著な臨床症状のひとつである<ref name="Hamada-2002-C&ED" />。皮膚にも病斑や瘢痕ができ、通常は顔面や手足に現れることが多い<ref name="Caro-1978" />。自然治癒力が低下し、加齢とともに瘢痕が増え続ける。皮膚は軽い外傷や怪我で簡単に損傷し、[[水疱|水ぶくれ]]や傷跡を残すことがある<ref name="Appenzeller-etal-2006-Neuroimaging16" />。また、通常、皮膚は非常に乾燥し、しわしわになる。白色または黄色の浸潤が口唇、頬粘膜、扁桃、口蓋垂、舌小帯に形成される<ref name="Caro-1978" />。その結果、上気道感染症を引き起こし、症状を緩和するために気管切開が必要になることもある<ref name="Hamada-2002-C&ED" />。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>
=== 神経系 ===
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