Examine individual changes

'{{Infobox medical condition (new) | name = Nakajo syndrome | image = Autosomal recessive - en.svg | caption = Nakajo syndrome has an autosomal recessive pattern of [[inheritance]]. | pronounce = | specialty = [[Medical genetics]] | synonyms =Nodular erythema with digital changes, Amyotrophy-fat tissue anomaly syndrome, Secondary hypertrophic osteoperiostosis with pernio | complications = | onset = | duration = | types = | causes = | risks = | diagnosis = | differential = | prevention = | treatment = | medication = | prognosis = | frequency = | deaths = }} '''Nakajo syndrome''', also called '''nodular erythema with digital changes''',<ref name=omim/> is a rare [[autosome|autosomal]] [[dominance (genetics)|recessive]] [[congenital disorder]] first reported in 1939 by A. Nakajo in the offspring of [[consanguineous]] (blood relative) parents.<ref>{{cite journal |author=Nakajo A |title=Secondary hypertrophic osteoperiostosis with pernio |language=Japanese |journal=J Derm Venerol. |volume=45 |pages=77–86 |year=1939}}</ref><ref name=nsar>{{cite journal | vauthors = Kitano Y, Matsunaga E, Morimoto T, Okada N, Sano S | title = A syndrome with nodular erythema, elongated and thickened fingers, and emaciation | journal = Archives of Dermatology | volume = 121 | issue = 8 | pages = 1053–1056 | date = August 1985 | pmid = 4026345 | doi = 10.1001/archderm.121.8.1053 }}</ref> The syndrome can be characterized by [[erythema]] (reddened skin), loss of [[adipose tissue|body fat]] in the upper part of the body, and disproportionately large eyes, ears, nose, lips, and fingers.<ref name=omim>{{OMIM|256040|Nakajo syndrome}}</ref> == Signs and symptoms == Signs of the disease begins during early childhood with individuals developing red, swollen lumps (nodular erythema) on the skin especially during colder weather, frequent fevers, and elongated fingers and toes with widened and rounded tips ([[Nail clubbing|clubbing]]).<ref name="medlineplus.gov"/> Later in childhood, individuals with the disease develop join pain, and joint deformities ([[contracture]]s) that limit movement predominantly in the hands, wrists, and elbows. They additional have weakness and wasting of muscle and fat loss that worsens over time. This leads to an extremely thin ([[Emaciation|emaciated]]) appearance in the face, chest, and arms.<ref name="medlineplus.gov"/>   Other symptoms of Nakajo-Nishimura syndrome are enlarged liver and spleen ([[hepatosplenomegaly]]), shortage of red blood cells ([[anemia]]), reduced levels of platelet blood cells ([[thrombocytopenia]]), and calcification in the basal ganglia area of the brain. There have been cases of intellectual disability in affected individuals.<ref name="medlineplus.gov"/> Nakajo-Nishimura syndrome has overlapping symptoms with joint contractures, muscular atrophy, microcytic anemia, and panniculitis-induced lipodystrophy (JMP) syndrome and chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome. These conditions are all caused by mutations in the [[PSMB8]] and characterized by skin abnormalities and [[lipodystrophy]]. Although these conditions are considered different diseases, some researchers believe they represent different forms of a single condition.<ref name="medlineplus.gov">{{Cite web |title=Nakajo-Nishimura syndrome: MedlinePlus Genetics |url=https://medlineplus.gov/genetics/condition/nakajo-nishimura-syndrome/ |access-date=2022-03-17 |website=medlineplus.gov |language=en}} {{PD-notice}}</ref> == Genetics == Nakajo syndrome is inherited in an [[Dominance (genetics)|autosomal recessive]] manner.<ref name=nsar/> This means the defective gene responsible for the disorder is located on an [[autosome]], and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. This gene is called PSMB8 and is located on chromosome 6 at 6p21.32.<ref>{{cite web | title = PSMB8 proteasome 20S subunit beta 8 [ Homo sapiens (human) ] | url = https://www.ncbi.nlm.nih.gov/gene/5696 | work = NCBI Gene | publisher = National Library of Medicine (US), National Center for Biotechnology Information }}</ref> This gene codes for a subunit called immunoproteasomes that are found immune system cells. These cells are crucial for identifying viral proteins. It has been noted that malfunctions in PSMB8 cause the destruction of proteins which leads to muscle degradation and fat loss. The parents of an individual with an autosomal recessive disorder both [[genetic carrier|carry]] one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.<ref name="medlineplus.gov" /> Although variations in severity has little clinical support, onset of Nakajo syndrome can vary from ages 1–18.<ref name=":0" /> ==Diagnosis== Typical diagnosis looks for at least 5 out of 8 proposed criteria for Nakajo Syndrome: an autosomal recessive inheritance pattern, pernio-like purplish lesions (on hands and feet), <nowiki>''</nowiki>haunting<nowiki>''</nowiki> nodular erythema, repetitive spiking fever, long clubbed fingers and toes with joint contractures, progressive upper body lipomuscular atrophy/emaciation, hepatosplenomegaly and basal ganglion calcification on computed tomography (CT) scans. These features are not always apparent until childhood. [[Histopathology|Histopathologic]] examination shows focal mononuclear cell infiltration with [[Vasculitis|vasculopathy]]. Laboratory results include continually elevated C-reactive protein (CRP) levels and [[Hypergammaglobulinemia|hyper-gamma-globulinemia]]. Autoantibody titers rise as the disease progresses in some but remain negative in others. Molecular genetic testing can detect a disease causing mutation, verifying diagnosis.<ref>{{Cite web |title=Nakajo Nishimura syndrome {{!}} Genetic and Rare Diseases Information Center (GARD) – an NCATS Program |url=https://rarediseases.info.nih.gov/diseases/3916/nakajo-nishimura-syndrome#:~:text=Diagnosis%20is%20based%20on%20the,joint%20contractures,%20progressive%20upper%20body |access-date=2022-03-21 |website=rarediseases.info.nih.gov}}</ref> == Management == Currently, there are no treatments for Nakajo syndrome. However, available treatment options may help alleviate some of the symptoms. Existing steroids may help reduce inflammatory responses. Various [[Immunosuppression|immunosuppressive]] and [[Disease-modifying antirheumatic drug|anti-rheumatic]] have shown to have little or no temporal response in PRAAS patients. Ultimately, the progressive [[lipodystrophy]] caused by Nakajo syndrome continues despite treatment.<ref>{{cite journal | vauthors = McDermott A, Jacks J, Kessler M, Emanuel PD, Gao L | title = Proteasome-associated autoinflammatory syndromes: advances in pathogeneses, clinical presentations, diagnosis, and management | journal = International Journal of Dermatology | volume = 54 | issue = 2 | pages = 121–129 | date = February 2015 | pmid = 25521013 | doi = 10.1111/ijd.12695 | s2cid = 205189155 }}</ref> == Epidemiology == Two affected siblings reported by Tanaka were born from a [[Consanguinity|consanguineous]] marriage.<ref>{{cite journal | vauthors = Tanaka M, Miyatani N, Yamada S, Miyashita K, Toyoshima I, Sakuma K, Tanaka K, Yuasa T, Miyatake T, Tsubaki T | display-authors = 6 | title = Hereditary lipo-muscular atrophy with joint contracture, skin eruptions and hyper-gamma-globulinemia: a new syndrome | journal = Internal Medicine | volume = 32 | issue = 1 | pages = 42–45 | date = January 1993 | pmid = 8495043 | doi = 10.2169/internalmedicine.32.42 }}</ref> Though a majority of cases originate in Japan, however two siblings reported by Garg were Portuguese and also born from a consanguineous marriage.<ref name=":0">{{cite journal | vauthors = Garg A, Hernandez MD, Sousa AB, Subramanyam L, Martínez de Villarreal L, dos Santos HG, Barboza O | title = An autosomal recessive syndrome of joint contractures, muscular atrophy, microcytic anemia, and panniculitis-associated lipodystrophy | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 95 | issue = 9 | pages = E58-E63 | date = September 2010 | pmid = 20534754 | pmc = 2936059 | doi = 10.1210/jc.2010-0488 }}</ref> == References == {{reflist}} == External links == {{Medical resources | ICD10 = L98.8 | ICD9 = | ICDO = | OMIM = 256040 | MedlinePlus = | eMedicineSubj = | eMedicineTopic = | MeshID = | Orphanet = 2615 }} [[Category:Autosomal recessive disorders]] [[Category:Congenital disorders]] [[Category:Rare diseases]] [[Category:Syndromes]] [[Category:Genetic disorders with OMIM but no gene]]'