{{Short description|A rare genetic disorder affecting the nervous system and other organs}}
| name = Arts syndrome
{{Medical genetics}}
| synonyms = ataxia-deafness-optic atrophy, lethal; ataxia - fatal x-linked with deafness and loss of vision
| image = X-linked recessive.svg
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| caption = This condition is inherited in an X-linked recessive manner
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'''Arts syndrome''' is a rare [[metabolic disorder]] that causes serious neurological problems in males due to a malfunction of the [[PRPP synthetase 1]] enzyme. Arts Syndrome is part of a spectrum of PRPS-1 related disorders with reduced activity of the enzyme that includes [[Charcot–Marie–Tooth disease]] and X-linked non-syndromic sensorineural deafness.<ref>{{Cite journal|last=Synofzik|first=Matthis|last2=Müller vom Hagen|first2=Jennifer|last3=Haack|first3=Tobias B|last4=Wilhelm|first4=Christian|last5=Lindig|first5=Tobias|last6=Beck-Wödl|first6=Stefanie|last7=Nabuurs|first7=Sander B|last8=van Kuilenburg|first8=André BP|last9=de Brouwer|first9=Arjan PM|date=2014-02-14|title=X-linked Charcot-Marie-Tooth disease, Arts syndrome, and prelingual non-syndromic deafness form a disease continuum: evidence from a family with a novel PRPS1 mutation|journal=Orphanet Journal of Rare Diseases|volume=9|pages=24|doi=10.1186/1750-1172-9-24|issn=1750-1172| pmc=3931488 |pmid=24528855}}</ref>
== Signs and symptoms ==
==Overview==
Males show more serious symptoms than females affected by this disorder.
'''Arts syndrome''' is a rare [[genetic disorder]] that primarily affects males. It is characterized by a combination of [[neurological]], [[developmental]], and [[metabolic]] abnormalities. The syndrome is caused by mutations in the [[PRPS1]] gene, which is located on the X chromosome, and follows an [[X-linked recessive]] inheritance pattern.
The symptoms for males are:
==Genetics==
# Profound sensorineural hearing loss i.e, a complete or almost complete loss of hearing caused by abnormalities in the inner ear.<ref name=":0">{{Cite journal|url=http://www.brainanddevelopment.com/article/S0387-7604(16)30058-4/abstract|title=Arts syndrome with a novel missense mutation in the PRPS1 gene: A case report|last=Maruyama|first=Koichi|date=November 2016|journal=Brain and Development|volume=38|issue=10|pages=954–958|access-date=10 March 2017|doi=10.1016/j.braindev.2016.05.003|pmid=27256512}}</ref>
Arts syndrome is caused by mutations in the [[PRPS1]] gene, which encodes the enzyme phosphoribosyl pyrophosphate synthetase 1. This enzyme is crucial for the synthesis of [[purines]], which are essential components of [[DNA]] and [[RNA]]. Mutations in this gene lead to a deficiency in enzyme activity, resulting in impaired purine synthesis and the clinical manifestations of the syndrome.
# Weak muscle tone - [[Hypotonia]].
# Impaired muscle coordination - [[Ataxia]].
# Developmental delay.
# Intellecual disability.
# Vision loss caused by optic nerve atrophy in early childhood.<ref name=":1">{{Cite journal|last=de Brouwer|first=Arjan P.M.|last2=van Bokhoven|first2=Hans|last3=Nabuurs|first3=Sander B.|last4=Arts|first4=Willem Frans|last5=Christodoulou|first5=John|last6=Duley|first6=John|date=2010-04-09|title=PRPS1 Mutations: Four Distinct Syndromes and Potential Treatment|journal=American Journal of Human Genetics|volume=86|issue=4|pages=506–518|doi=10.1016/j.ajhg.2010.02.024|issn=0002-9297| pmc=2850427 |pmid=20380929}}</ref>
# [[Peripheral neuropathy]].
# Recurrent infections, especially in the respiratory system.
# Muscle weakness caused by recurrent infections.
Symptoms for females:
Very rarely seen hearing loss that begins in adulthood (age > 20 years) combined with [[ataxia]] and neuropathy. Optic atrophy and [[retinitis pigmentosa]] <ref name="Kelley 827–838">{{Cite book|last=Kelley|first=Roger E.|last2=Andersson|first2=Hans C.|date=2014-01-01|title=Disorders of purines and pyrimidines|journal=Handbook of Clinical Neurology|volume=120|pages=827–838|doi=10.1016/B978-0-7020-4087-0.00055-3|issn=0072-9752|pmid=24365355|isbn=9780702040870}}</ref> observed in some cases too.<ref name="Moran 455–460">{{Cite journal|last=Moran|first=Rocio|last2=Kuilenburg|first2=André B. P.|last3=Duley|first3=John|last4=Nabuurs|first4=Sander B.|last5=Retno-Fitri|first5=Aditia|last6=Christodoulou|first6=John|last7=Roelofsen|first7=Jeroen|last8=Yntema|first8=Helger G.|last9=Friedman|first9=Neil R.|date=2012-02-01|title=Phosphoribosylpyrophosphate synthetase superactivity and recurrent infections is caused by a p.Val142Leu mutation in PRS-I|journal=American Journal of Medical Genetics. Part A|volume=158A|issue=2|pages=455–460|doi=10.1002/ajmg.a.34428|issn=1552-4833|pmid=22246954}}</ref>
==Clinical Features==
The clinical features of Arts syndrome can vary but typically include:
== Cause ==
* [[Sensorineural hearing loss]]
Arts syndrome is caused by a loss of function mutation in the PRPS1 gene.<ref name="Moran 455–460"/> The PRPS1 gene codes for the enzyme phosphoribosyl pyrophosphate synthetase 1 or PRPP synthetase 1. This enzyme is involved in producing purines and pyrimidines which are the building blocks of DNA, RNA, ATP and other molecules. The mutations that cause Arts syndrome replace single amino acids the PRPP synthetase 1 enzyme.<ref>{{Cite journal|last=Pei|first=Wuhong|last2=Xu|first2=Lisha|last3=Varshney|first3=Gaurav K.|last4=Carrington|first4=Blake|last5=Bishop|first5=Kevin|last6=Jones|first6=MaryPat|last7=Huang|first7=Sunny C.|last8=Idol|first8=Jennifer|last9=Pretorius|first9=Pamela R.|date=2016-07-18|title=Additive reductions in zebrafish PRPS1 activity result in a spectrum of deficiencies modeling several human PRPS1-associated diseases|journal=Scientific Reports|volume=6|pages=29946|doi=10.1038/srep29946|issn=2045-2322| pmc=4947902 |pmid=27425195|bibcode=2016NatSR...629946P}}</ref> The resulting enzyme is unstable. Disruption of purine and pyrimidine production may impair energy storage and transport in cells. Impairment of these processes may have a particularly severe effect on tissues that require a large amount of energy, such as the nervous system, resulting in the neurological problems characteristic of Arts syndrome. The reason for the increased risk of respiratory infections in Arts syndrome is unclear.
Affected individuals may also experience [[hypotonia]] and [[delayed motor development]].
c.455T→C (p. L152P), c.398A→C (p.Q133P) <ref name=":2">{{Cite journal|last=de Brouwer|first=Arjan P. M.|last2=Williams|first2=Kelly L.|last3=Duley|first3=John A.|last4=van Kuilenburg|first4=André B. P.|last5=Nabuurs|first5=Sander B.|last6=Egmont-Petersen|first6=Michael|last7=Lugtenberg|first7=Dorien|last8=Zoetekouw|first8=Lida|last9=Banning|first9=Martijn J. G.|date=2017-03-10|title=Arts Syndrome Is Caused by Loss-of-Function Mutations in PRPS1|journal=American Journal of Human Genetics|volume=81|issue=3|pages=507–518|doi=10.1086/520706|issn=0002-9297| pmc=1950830 |pmid=17701896}}</ref>
==Diagnosis==
Diagnosis of Arts syndrome is based on clinical evaluation, family history, and genetic testing to identify mutations in the [[PRPS1]] gene. [[Audiometry]] and [[neurological examination]] are often part of the diagnostic process.
p. Ile275Thr and p.Gly306Glu <ref>{{Cite journal|last=Gandía|first=Marta|last2=Fernández-Toral|first2=Joaquín|last3=Solanellas|first3=Juan|last4=Domínguez-Ruiz|first4=María|last5=Gómez-Rosas|first5=Elena|last6=Del Castillo|first6=Francisco J.|last7=Villamar|first7=Manuela|last8=Moreno-Pelayo|first8=Miguel A.|last9=Del Castillo|first9=Ignacio|date=2015-07-01|title=Mutations in PRPS1 causing syndromic or nonsyndromic hearing impairment: intrafamilial phenotypic variation complicates genetic counseling|journal=Pediatric Research|volume=78|issue=1|pages=97–102|doi=10.1038/pr.2015.56|issn=1530-0447|pmid=25785835|doi-access=free}}</ref>
==Management==
There is currently no cure for Arts syndrome, and management focuses on symptomatic treatment and supportive care. This may include:
== Genetics==
* [[Hearing aids]] or [[cochlear implants]] for hearing loss
Arts syndrome follows an X-linked inheritance. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell sometimes causes features of the disorder; in other cases, these females do not experience any symptoms. In the small number of Arts syndrome cases that have been identified, affected individuals have inherited the mutation from a mother who carries an altered copy of the PRPS1 gene. If the mother is a carrier, the chance of transmitting the ''PRPS1'' mutation in each pregnancy is 50%. Males who inherit the mutation will be affected; females who inherit the mutation will be carriers and may or may not be mildly affected. Males with Arts syndrome do not reproduce.<ref name=":3">{{Cite book|chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK2591/|title=GeneReviews|last=de Brouwer|first=Arjan PM|last2=Duley|first2=John A.|last3=Christodoulou|first3=John|date=1993-01-01|publisher=University of Washington, Seattle|editor-last=Pagon|editor-first=Roberta A.|location=Seattle (WA)|pmid=20301738|editor-last2=Adam|editor-first2=Margaret P.|editor-last3=Ardinger|editor-first3=Holly H.|editor-last4=Wallace|editor-first4=Stephanie E.|editor-last5=Amemiya|editor-first5=Anne|editor-last6=Bean|editor-first6=Lora JH|editor-last7=Bird|editor-first7=Thomas D.|editor-last8=Ledbetter|editor-first8=Nikki|editor-last9=Mefford|editor-first9=Heather C.|chapter=Arts Syndrome}}</ref>
* [[Physical therapy]] for motor difficulties
* [[Occupational therapy]] to improve daily living skills
Charcot-Marie-Tooth disease-5, Arts syndrome and X-linked nonsyndromic sensorineural deafness present three clinically distinct but genetically allelic disorders, caused by reduced phosphoribosylpyrophosphate synthetase 1 (PRS1) activity due to PRPS1 mutations. Only three families with CMTX5 and two families Arts syndrome, respectively, have been reported worldwide so far. Thus, evidence is still rare whether these two disorders are separate entities, or rather clusters on a phenotypic continuum of PRPS1-related disease.
==Prognosis==
The prognosis for individuals with Arts syndrome varies depending on the severity of symptoms. Early intervention and supportive therapies can improve quality of life, but the condition is progressive and can lead to significant disability.
== Diagnosis ==
==Related pages==
Arts syndrome should be included in the differential diagnosis of infantile hypotonia and weakness aggravated by recurrent infection with a family history of X-linked inheritance. Sequence analysis of PRPS1, the only gene associated with Arts syndrome, has detected mutations in both kindreds reported to date. Arts syndrome patients were also found to have reduced levels of hypoxanthine levels in urine and uric acid levels in the serum.<ref name=":2" /> In vitro, PRS-1 activity was reduced in erythrocytes and fibroblasts.
* [[X-linked recessive inheritance]]
* [[Genetic disorders]]
* [[Neurological disorders]]
== Treatment ==
[[Category:Genetic disorders]]
Currently, purine replacement via S-adenosylmethionine (SAM) supplementation in people with Arts syndrome appears to improve their condition. This suggests that SAM supplementation can alleviate symptoms of PRPS1 deficient patients by replacing purine nucleotides <ref name=":1" /> and open new avenues of therapeutic intervention.<ref name=":2" /><ref>{{Cite journal|last=Mittal|first=Rahul|last2=Patel|first2=Kunal|last3=Mittal|first3=Jeenu|last4=Chan|first4=Brandon|last5=Yan|first5=Denise|last6=Grati|first6=M'hamed|last7=Liu|first7=Xue Zhong|date=2015-01-01|title=Association of PRPS1 Mutations with Disease Phenotypes|journal=Disease Markers|volume=2015|pages=127013|doi=10.1155/2015/127013|issn=0278-0240| pmc=4458296 |pmid=26089585}}</ref> Other non-clinical treatment options include educational programs tailored to their individual needs. Sensorineural hearing loss has been treated with cochlear implantation with good results. Ataxia and visual impairment from optic atrophy are treated in a routine manner. Routine immunizations against common childhood infections and annual influenza immunization can also help prevent any secondary infections from occurring.
Regular neuropsychological, audiologic, and ophthalmologic examinations are also recommended.
Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the disease-causing mutation in the family is known.<ref name="Kelley 827–838"/><ref name=":3" />
==References==
{{Reflist}}
== External links ==
{{Medical resources
| ICD10 = E79.8
| ICD9 = <!--{{ICD9|xxx}}-->
| ICDO =
| OMIM = 301835
| DiseasesDB =
| MedlinePlus =
| eMedicineSubj =
| eMedicineTopic =
| MeSH = C535388
| GeneReviewsNBK =
| GeneReviewsName =
| Orphanet = 1187
}}
[[Category:Metabolic disorders]]
[[Category:Neurological disorders]]
[[Category:Neurological disorders]]
[[Category:Medical genetics]]
[[Category:Rare syndromes]]
[[Category:Syndromes affecting muscles]]
[[Category:Syndromes affecting the nervous system]]
[[Category:Syndromes with sensorineural hearing loss]]
{{dictionary-stub1}}
Revision as of 11:45, 15 February 2025
A rare genetic disorder affecting the nervous system and other organs
Arts syndrome is a rare genetic disorder that primarily affects males. It is characterized by a combination of neurological, developmental, and metabolic abnormalities. The syndrome is caused by mutations in the PRPS1 gene, which is located on the X chromosome, and follows an X-linked recessive inheritance pattern.
Genetics
Arts syndrome is caused by mutations in the PRPS1 gene, which encodes the enzyme phosphoribosyl pyrophosphate synthetase 1. This enzyme is crucial for the synthesis of purines, which are essential components of DNA and RNA. Mutations in this gene lead to a deficiency in enzyme activity, resulting in impaired purine synthesis and the clinical manifestations of the syndrome.
Clinical Features
The clinical features of Arts syndrome can vary but typically include:
Diagnosis of Arts syndrome is based on clinical evaluation, family history, and genetic testing to identify mutations in the PRPS1 gene. Audiometry and neurological examination are often part of the diagnostic process.
Management
There is currently no cure for Arts syndrome, and management focuses on symptomatic treatment and supportive care. This may include:
The prognosis for individuals with Arts syndrome varies depending on the severity of symptoms. Early intervention and supportive therapies can improve quality of life, but the condition is progressive and can lead to significant disability.
