Canavan disease: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
No edit summary
 
(66 intermediate revisions by the same user not shown)
Line 3: Line 3:
{{CMG}}; {{AE}} {{ZMalik}}  
{{CMG}}; {{AE}} {{ZMalik}}  


 
{{SK}} [[Aspartoacylase Deficiency]], [[Canavan–van Bogaert–Bertrand disease]], [[ASPA Deficiency]], [[Canavan's leukodystrophy]]
{{SK}}  


'''For patient information, click [[Canavan disease (patient information)|here]]'''
'''For patient information, click [[Canavan disease (patient information)|here]]'''
Line 24: Line 23:


==Overview==
==Overview==
 
Canavan disease is a rare [[autosomal recessive]] degenerative disease with fatal neurological deficits that begins in infancy and has rapid progression. It is a [[leukodystrophy]] with deficiency of [[enzyme]] [[aspartoacylase]] causing accumulation of [[N-acetylaspartic acid]]. It is characterized by abnormal [[myelination]] and [[white matter]] atrophy.


==Historical Perspective==
==Historical Perspective==
Line 44: Line 43:


==Causes==
==Causes==
* This [[autosomal recessive]] disease is caused by [[mutation]] in [[ASPA]] [[gene]] on [[chromosome 17]] responsible for [[aspartoacylase]] enzyme production.<ref name="von JonquieresSpencer2017">{{cite journal|last1=von Jonquieres|first1=Georg|last2=Spencer|first2=Ziggy H. T.|last3=Rowlands|first3=Benjamin D.|last4=Klugmann|first4=Claudia B.|last5=Bongers|first5=Andre|last6=Harasta|first6=Anne E.|last7=Parley|first7=Kristina E.|last8=Cederholm|first8=Jennie|last9=Teahan|first9=Orla|last10=Pickford|first10=Russell|last11=Delerue|first11=Fabien|last12=Ittner|first12=Lars M.|last13=Fröhlich|first13=Dominik|last14=McLean|first14=Catriona A.|last15=Don|first15=Anthony S.|last16=Schneider|first16=Miriam|last17=Housley|first17=Gary D.|last18=Rae|first18=Caroline D.|last19=Klugmann|first19=Matthias|title=Uncoupling N-acetylaspartate from brain pathology: implications for Canavan disease gene therapy|journal=Acta Neuropathologica|volume=135|issue=1|year=2017|pages=95–113|issn=0001-6322|doi=10.1007/s00401-017-1784-9}}</ref>
* This [[autosomal recessive]] disease is caused by [[mutation]] in [[ASPA]] [[gene]] on short arm of [[chromosome 17]] responsible for [[aspartoacylase]] enzyme production.<ref name="von JonquieresSpencer2017">{{cite journal|last1=von Jonquieres|first1=Georg|last2=Spencer|first2=Ziggy H. T.|last3=Rowlands|first3=Benjamin D.|last4=Klugmann|first4=Claudia B.|last5=Bongers|first5=Andre|last6=Harasta|first6=Anne E.|last7=Parley|first7=Kristina E.|last8=Cederholm|first8=Jennie|last9=Teahan|first9=Orla|last10=Pickford|first10=Russell|last11=Delerue|first11=Fabien|last12=Ittner|first12=Lars M.|last13=Fröhlich|first13=Dominik|last14=McLean|first14=Catriona A.|last15=Don|first15=Anthony S.|last16=Schneider|first16=Miriam|last17=Housley|first17=Gary D.|last18=Rae|first18=Caroline D.|last19=Klugmann|first19=Matthias|title=Uncoupling N-acetylaspartate from brain pathology: implications for Canavan disease gene therapy|journal=Acta Neuropathologica|volume=135|issue=1|year=2017|pages=95–113|issn=0001-6322|doi=10.1007/s00401-017-1784-9}}</ref>


==Differentiating {{PAGENAME}} from Other Diseases==
==Differentiating {{PAGENAME}} from Other Diseases==
*Canavan disease must be differentiated from other dysmylinating diseases that affect the [[white matter]] such as:
**[[Adrenoleukodystrophy]]
**[[Metachromatic leukodystrophy]]
**[[Pelizaeus-Merzbacher disease]]
**[[Alexander disease]]


==Epidemiology and Demographics==
==Epidemiology and Demographics==
*The [[prevalence]] of Canavan Disease is approximately 1 per 100,000 individuals in general population.<ref name="ReddyCalloni2018">{{cite journal|last1=Reddy|first1=Nihaal|last2=Calloni|first2=Sonia F.|last3=Vernon|first3=Hilary J.|last4=Boltshauser|first4=Eugen|last5=Huisman|first5=Thierry A. G. M.|last6=Soares|first6=Bruno P.|title=Neuroimaging Findings of Organic Acidemias and Aminoacidopathies|journal=RadioGraphics|volume=38|issue=3|year=2018|pages=912–931|issn=0271-5333|doi=10.1148/rg.2018170042}}</ref>
*Canavan disease usually affects individuals of the Eastern European (Ashkenazi) Jewish ancestry.
*In Ashkenazi Jews the [[prevalence]] of this disease is 1 in 6000-14000 individuals and 1 in 37-57 individuals are [[carriers]] among this population.<ref name="Zayed2015">{{cite journal|last1=Zayed|first1=Hatem|title=Canavan disease: An Arab scenario|journal=Gene|volume=560|issue=1|year=2015|pages=9–14|issn=03781119|doi=10.1016/j.gene.2015.02.009}}</ref>


==Risk Factors==
==Risk Factors==
*There are no established risk factors for Canavan disease.<ref name="von JonquieresSpencer2017">{{cite journal|last1=von Jonquieres|first1=Georg|last2=Spencer|first2=Ziggy H. T.|last3=Rowlands|first3=Benjamin D.|last4=Klugmann|first4=Claudia B.|last5=Bongers|first5=Andre|last6=Harasta|first6=Anne E.|last7=Parley|first7=Kristina E.|last8=Cederholm|first8=Jennie|last9=Teahan|first9=Orla|last10=Pickford|first10=Russell|last11=Delerue|first11=Fabien|last12=Ittner|first12=Lars M.|last13=Fröhlich|first13=Dominik|last14=McLean|first14=Catriona A.|last15=Don|first15=Anthony S.|last16=Schneider|first16=Miriam|last17=Housley|first17=Gary D.|last18=Rae|first18=Caroline D.|last19=Klugmann|first19=Matthias|title=Uncoupling N-acetylaspartate from brain pathology: implications for Canavan disease gene therapy|journal=Acta Neuropathologica|volume=135|issue=1|year=2017|pages=95–113|issn=0001-6322|doi=10.1007/s00401-017-1784-9}}</ref>
*It is an [[autosomal recessive]] disease.
*It is more common in the Ashkenazi Jew population.<ref name="Zayed2015">{{cite journal|last1=Zayed|first1=Hatem|title=Canavan disease: An Arab scenario|journal=Gene|volume=560|issue=1|year=2015|pages=9–14|issn=03781119|doi=10.1016/j.gene.2015.02.009}}</ref>


==Screening==
==Screening==
*There is insufficient evidence to recommend routine [[screening]] for Canavan disease in the general population.
*Carrier testing is suggested for people of Northern and Central Europe.
*[[Prenatal]] screening is done in high-risk cases.<ref name="MatalonMatalon2002">{{cite journal|last1=Matalon|first1=Reuben|last2=Matalon|first2=Kimberlee Michals|title=Canavan disease|journal=Obstetrics and Gynecology Clinics of North America|volume=29|issue=2|year=2002|pages=297–304|issn=08898545|doi=10.1016/S0889-8545(01)00003-1}}</ref>


==Natural History, Complications, and Prognosis==
==Natural History, Complications, and Prognosis==
*Patients with Canavan disease may progress to develop life-threatening complications, some patients may develop earlier in the infant stage and some develop later.
*Common complications of Canavan disease include:
**Delayed/lack of [[motor skills]]
**[[Hypotonia]] that may progress to [[spasticity]] and [[seizures]]
**Swallowing difficulty
**[[Paralysis]]
**[[Optic atrophy]] leading to blindness
**Death
*Prognosis is generally poor in the most common form of the disease, and patients usually don't survive beyond age ten. Some patients may survive into teens and twenties. Patients with a mild form of the disease have a normal lifespan.


==Diagnosis==
==Diagnosis==
===Diagnostic Study of Choice===
===Diagnostic Study of Choice===
*There are no established criteria for the diagnosis of Canavan disease. However, the diagnosis is confirmed by the presence of increased urinary [[N-acetylaspartic acid]] and an [[MRI]] suggestive of [[white matter]] disease in patients presenting with the aforementioned signs and symptoms.<ref name="ReddyCalloni2018">{{cite journal|last1=Reddy|first1=Nihaal|last2=Calloni|first2=Sonia F.|last3=Vernon|first3=Hilary J.|last4=Boltshauser|first4=Eugen|last5=Huisman|first5=Thierry A. G. M.|last6=Soares|first6=Bruno P.|title=Neuroimaging Findings of Organic Acidemias and Aminoacidopathies|journal=RadioGraphics|volume=38|issue=3|year=2018|pages=912–931|issn=0271-5333|doi=10.1148/rg.2018170042}}</ref>


===History and Symptoms===
===History and Symptoms===
*Most commonly patients present at three to six months of age with lethargy, weak cry, irritability, poor head control, [[macrocephaly]], [[hypotonia]], poor feeding due to dysfunctional swallowing, [[seizures]]. The disease have relentless progression and soon is complicated by blindness, [[spasticity]], [[decerebrate posturing]] and eventual death.<ref name="TraegerRapin1998">{{cite journal|last1=Traeger|first1=Eveline C.|last2=Rapin|first2=Isabelle|title=The Clinical Course of Canavan Disease|journal=Pediatric Neurology|volume=18|issue=3|year=1998|pages=207–212|issn=08878994|doi=10.1016/S0887-8994(97)00185-9}}</ref>
*The late-onset variant of the disease has mild and non-specific signs and symptoms including speech delay and motor skill delay. It usually presents after 5 years of age and have normal life expectancy.


===Physical Examination===
===Physical Examination===
*Common physical examination findings of Canavan disease include [[hypotonia]], poor head control, [[macrocephaly]], poor visual tracking, delayed [[motor skills]], and/or irritability. As the disease advances, [[hypotonia]] progresses to [[spasticity]] and [[hyperreflexia]].


===Laboratory Findings===
===Laboratory Findings===
* An elevated concentration of urinary [[N-acetyl aspartate]] (NAA) aids in the diagnosis of Canavan disease.<ref name="ReddyCalloni2018">{{cite journal|last1=Reddy|first1=Nihaal|last2=Calloni|first2=Sonia F.|last3=Vernon|first3=Hilary J.|last4=Boltshauser|first4=Eugen|last5=Huisman|first5=Thierry A. G. M.|last6=Soares|first6=Bruno P.|title=Neuroimaging Findings of Organic Acidemias and Aminoacidopathies|journal=RadioGraphics|volume=38|issue=3|year=2018|pages=912–931|issn=0271-5333|doi=10.1148/rg.2018170042}}</ref>
* An elevated concentration of [[amniotic fluid]] [[N-acetyl aspartate]] (NAA) and/or [[enzyme assay]] of [[aspartoacylase]] in [[amniotic cells]] and [[chorionic villi]] is used for [[prenatal]] diagnosis of Canavan disease.<ref name="MatalonMichals1988">{{cite journal|last1=Matalon|first1=R.|last2=Michals|first2=K.|last3=Sebesta|first3=D.|last4=Deanching|first4=M.|last5=Gashkoff|first5=P.|last6=Casanova|first6=J.|last7=Optiz|first7=John M.|last8=Reynolds|first8=James F.|title=Aspartoacylase deficiency and N-acetylaspartic aciduria in patients with canavan disease|journal=American Journal of Medical Genetics|volume=29|issue=2|year=1988|pages=463–471|issn=0148-7299|doi=10.1002/ajmg.1320290234}}</ref>


===Electrocardiogram===
===Electrocardiogram===
*There are no ECG findings associated with Canavan disease.


===X-ray===
===X-ray===
*There are no x-ray findings associated with Canavan disease.


===Echocardiography or Ultrasound===
===Echocardiography or Ultrasound===
*There are no echocardiography/ultrasound findings associated with Canavan disease.


===CT scan===
===CT scan===
*Early-stage CT shows [[macrencephaly]] with decreased subcortical [[white matter]] attenuation without post-contrast enhancement.
*CT scan obtained at late-stage shows [[cortical atrophy]] suggested by ventricular dilation and prominent sulci and [[basal cisterns]]. <ref name="pmid11589315">{{cite journal| author=Gordon N| title=Canavan disease: a review of recent developments. | journal=Eur J Paediatr Neurol | year= 2001 | volume= 5 | issue= 2 | pages= 65-9 | pmid=11589315 | doi=10.1053/ejpn.2001.0467 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11589315  }} </ref>


===MRI===
===MRI===
*[[MRI]] confirms an enlarged brain. T1 weighted images show areas of low signal intensity and T2 weighted images show high signal intensity areas within the [[white matter]]. [[Globus pallidus]] and [[thalamus]] is also involved while MRI shows sparing of [[internal capsule]], [[caudate nucleus]]. [[putamen]] and [[corpus callosum]].
*[[MRI]] done in late-stage shows periventricular [[white matter]] atrophy.


===Imaging Findings===
===Imaging Findings===
[[MR spectroscopy]] is helpful in the diagnosis of Canavan disease. Findings on [[MR spectroscopy]] diagnostic of Canavan disease include elevated NAA and NAA:creatine ratio.<ref name="pmid29757724">{{cite journal| author=Reddy N, Calloni SF, Vernon HJ, Boltshauser E, Huisman TAGM, Soares BP| title=Neuroimaging Findings of Organic Acidemias and Aminoacidopathies. | journal=Radiographics | year= 2018 | volume= 38 | issue= 3 | pages= 912-931 | pmid=29757724 | doi=10.1148/rg.2018170042 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29757724  }} </ref>


===Other Diagnostic Studies===
===Other Diagnostic Studies===
*There are no other diagnostic studies associated with Canavan disease.


==Treatment==
==Treatment==


===Medical Therapy===
===Medical Therapy===
*There is no treatment for Canavan disease; the mainstay of therapy is supportive care:
**Adequate nutrition and hydration support with [[gastrostomy]]
**[[Physical therapy]] for delayed/lacking [[motor skills]]
**[[Antiepileptic drugs]] for [[seizure]] control
**[[Gastrostomy]] tube also decreases the risk of [[aspiration]]
**[[Botulinum toxin]] can help [[spasticity]]
**Special programs to help with communication skills.<ref name="HoshinoKubota2014">{{cite journal|last1=Hoshino|first1=Hideki|last2=Kubota|first2=Masaya|title=Canavan disease: Clinical features and recent advances in research|journal=Pediatrics International|volume=56|issue=4|year=2014|pages=477–483|issn=13288067|doi=10.1111/ped.12422}}</ref> <ref name="pmid23449113">{{cite journal| author=Nagabhushan Kalburgi S, Khan NN, Gray SJ| title=Recent gene therapy advancements for neurological diseases. | journal=Discov Med | year= 2013 | volume= 15 | issue= 81 | pages= 111-9 | pmid=23449113 | doi= | pmc=5554939 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23449113  }} </ref>
*Experimental Treatment under research:
**[[Lithium citrate]]: Aimed at decreasing level of N-acetyl aspartate.<ref name="AssadiJanson2010">{{cite journal|last1=Assadi|first1=Mitra|last2=Janson|first2=Christopher|last3=Wang|first3=Dah-Jyuu|last4=Goldfarb|first4=Olga|last5=Suri|first5=Neeti|last6=Bilaniuk|first6=Larissa|last7=Leone|first7=Paola|title=Lithium citrate reduces excessive intra-cerebral N-acetyl aspartate in Canavan disease|journal=European Journal of Paediatric Neurology|volume=14|issue=4|year=2010|pages=354–359|issn=10903798|doi=10.1016/j.ejpn.2009.11.006}}</ref>
**[[Gene]] Therapy: Aimed at replacing defective gene with a healthy one.<ref name="JansonMcPhee2002">{{cite journal|last1=Janson|first1=Christopher|last2=McPhee|first2=Scott|last3=Bilaniuk|first3=Larissa|last4=Haselgrove|first4=John|last5=Testaiuti|first5=Mark|last6=Freese|first6=Andrew|last7=Wang|first7=Dah-Jyuu|last8=Shera|first8=David|last9=Hurh|first9=Peter|last10=Rupin|first10=Joan|last11=Saslow|first11=Elizabeth|last12=Goldfarb|first12=Olga|last13=Goldberg|first13=Michael|last14=Larijani|first14=Ghassem|last15=Sharrar|first15=William|last16=Liouterman|first16=Larisa|last17=Camp|first17=Angelique|last18=Kolodny|first18=Edwin|last19=Samulski|first19=Jude|last20=Leone|first20=Paola|title=Gene Therapy of Canavan Disease: AAV-2 Vector for Neurosurgical Delivery of Aspartoacylase Gene (ASPA) to the Human Brain|journal=Human Gene Therapy|volume=13|issue=11|year=2002|pages=1391–1412|issn=1043-0342|doi=10.1089/104303402760128612}}</ref> The results showed improvement in life of the patient without adverse effects during 5-year follow-up.<ref name="LeoneShera2012">{{cite journal|last1=Leone|first1=P.|last2=Shera|first2=D.|last3=McPhee|first3=S. W. J.|last4=Francis|first4=J. S.|last5=Kolodny|first5=E. H.|last6=Bilaniuk|first6=L. T.|last7=Wang|first7=D.-J.|last8=Assadi|first8=M.|last9=Goldfarb|first9=O.|last10=Goldman|first10=H. W.|last11=Freese|first11=A.|last12=Young|first12=D.|last13=During|first13=M. J.|last14=Samulski|first14=R. J.|last15=Janson|first15=C. G.|title=Long-Term Follow-Up After Gene Therapy for Canavan Disease|journal=Science Translational Medicine|volume=4|issue=165|year=2012|pages=165ra163–165ra163|issn=1946-6234|doi=10.1126/scitranslmed.3003454}}</ref>


===Surgery===
===Surgery===
*Surgical intervention is not recommended for the management of Canavan disease.


===Primary Prevention===
===Primary Prevention===
*Effective measures for the primary prevention of Canavan disease include [[carrier]] testing and [[genetic]] counseling in high-risk individuals/populations.


===Secondary Prevention===
===Secondary Prevention===
 
*There are no established measures for the secondary prevention of Canavan Disease.
 
==See also==
*[[The Myelin Project]]
*[[The Stennis Foundation]]
 
==External links==
* [http://www.ninds.nih.gov/disorders/canavan/canavan.htm Information on the disorder from the National Institute of Neurological Disorder and Stroke]
* [http://www4.umdnj.edu/cgtcweb/ Cell & Gene Therapy Center at UMDNJ]
* [http://www.beatcanavan.org/ Beat Canavan Disease - A web site dedicated to raising funds to save a Canavan baby's life]
* [http://www.canavanresearch.org/ Canavan Research Illinois - A public charity devoted to curing Canavan disease]
* [http://www.canavan.org/ Canavan Research - A foundation devoted to curing Canavan disease]
* [http://www.jacobscure.org/ Jacob's Cure - A non-profit organization dedicated to raising money for Canavan disease research]


==References==
==References==

Latest revision as of 21:21, 14 August 2020

WikiDoc Resources for Canavan disease

Articles

Most recent articles on Canavan disease

Most cited articles on Canavan disease

Review articles on Canavan disease

Articles on Canavan disease in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Canavan disease

Images of Canavan disease

Photos of Canavan disease

Podcasts & MP3s on Canavan disease

Videos on Canavan disease

Evidence Based Medicine

Cochrane Collaboration on Canavan disease

Bandolier on Canavan disease

TRIP on Canavan disease

Clinical Trials

Ongoing Trials on Canavan disease at Clinical Trials.gov

Trial results on Canavan disease

Clinical Trials on Canavan disease at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Canavan disease

NICE Guidance on Canavan disease

NHS PRODIGY Guidance

FDA on Canavan disease

CDC on Canavan disease

Books

Books on Canavan disease

News

Canavan disease in the news

Be alerted to news on Canavan disease

News trends on Canavan disease

Commentary

Blogs on Canavan disease

Definitions

Definitions of Canavan disease

Patient Resources / Community

Patient resources on Canavan disease

Discussion groups on Canavan disease

Patient Handouts on Canavan disease

Directions to Hospitals Treating Canavan disease

Risk calculators and risk factors for Canavan disease

Healthcare Provider Resources

Symptoms of Canavan disease

Causes & Risk Factors for Canavan disease

Diagnostic studies for Canavan disease

Treatment of Canavan disease

Continuing Medical Education (CME)

CME Programs on Canavan disease

International

Canavan disease en Espanol

Canavan disease en Francais

Business

Canavan disease in the Marketplace

Patents on Canavan disease

Experimental / Informatics

List of terms related to Canavan disease

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Zehra Malik, M.B.B.S[2]

Synonyms and keywords: Aspartoacylase Deficiency, Canavan–van Bogaert–Bertrand disease, ASPA Deficiency, Canavan's leukodystrophy

For patient information, click here

Canavan disease
ICD-9 330.0
OMIM 271900
DiseasesDB 29780
MedlinePlus 001586

Overview

Canavan disease is a rare autosomal recessive degenerative disease with fatal neurological deficits that begins in infancy and has rapid progression. It is a leukodystrophy with deficiency of enzyme aspartoacylase causing accumulation of N-acetylaspartic acid. It is characterized by abnormal myelination and white matter atrophy.

Historical Perspective

  • Canavan disease was first described in 1931 by an American neuropathologist, Myrtelle Canavan.[1]
  • She wrote a case-study in 1931 of a child who died at sixteen-month of age and was found to have cerebral spongy degenerative changes of the central nervous system.[1]
  • The disease was later named after Myrtelle Canavan.

Classification

  • There is no established system for the classification of Canavan disease.
  • Canavan disease is categorized as a leukodystrophy.[2]

Pathophysiology

Causes

Differentiating Canavan disease from Other Diseases

Epidemiology and Demographics

  • The prevalence of Canavan Disease is approximately 1 per 100,000 individuals in general population.[5]
  • Canavan disease usually affects individuals of the Eastern European (Ashkenazi) Jewish ancestry.
  • In Ashkenazi Jews the prevalence of this disease is 1 in 6000-14000 individuals and 1 in 37-57 individuals are carriers among this population.[6]

Risk Factors

  • There are no established risk factors for Canavan disease.[4]
  • It is an autosomal recessive disease.
  • It is more common in the Ashkenazi Jew population.[6]

Screening

  • There is insufficient evidence to recommend routine screening for Canavan disease in the general population.
  • Carrier testing is suggested for people of Northern and Central Europe.
  • Prenatal screening is done in high-risk cases.[7]

Natural History, Complications, and Prognosis

  • Patients with Canavan disease may progress to develop life-threatening complications, some patients may develop earlier in the infant stage and some develop later.
  • Common complications of Canavan disease include:
  • Prognosis is generally poor in the most common form of the disease, and patients usually don't survive beyond age ten. Some patients may survive into teens and twenties. Patients with a mild form of the disease have a normal lifespan.

Diagnosis

Diagnostic Study of Choice

  • There are no established criteria for the diagnosis of Canavan disease. However, the diagnosis is confirmed by the presence of increased urinary N-acetylaspartic acid and an MRI suggestive of white matter disease in patients presenting with the aforementioned signs and symptoms.[5]

History and Symptoms

  • Most commonly patients present at three to six months of age with lethargy, weak cry, irritability, poor head control, macrocephaly, hypotonia, poor feeding due to dysfunctional swallowing, seizures. The disease have relentless progression and soon is complicated by blindness, spasticity, decerebrate posturing and eventual death.[8]
  • The late-onset variant of the disease has mild and non-specific signs and symptoms including speech delay and motor skill delay. It usually presents after 5 years of age and have normal life expectancy.

Physical Examination

Laboratory Findings

Electrocardiogram

  • There are no ECG findings associated with Canavan disease.

X-ray

  • There are no x-ray findings associated with Canavan disease.

Echocardiography or Ultrasound

  • There are no echocardiography/ultrasound findings associated with Canavan disease.

CT scan

MRI

Imaging Findings

MR spectroscopy is helpful in the diagnosis of Canavan disease. Findings on MR spectroscopy diagnostic of Canavan disease include elevated NAA and NAA:creatine ratio.[10]

Other Diagnostic Studies

  • There are no other diagnostic studies associated with Canavan disease.

Treatment

Medical Therapy

Surgery

  • Surgical intervention is not recommended for the management of Canavan disease.

Primary Prevention

  • Effective measures for the primary prevention of Canavan disease include carrier testing and genetic counseling in high-risk individuals/populations.

Secondary Prevention

  • There are no established measures for the secondary prevention of Canavan Disease.

References

  1. ↑ 1.0 1.1 Canavan, Myrtelle M. (1931). "SCHILDER'S ENCEPHALITIS PERIAXIALIS DIFFUSA". Archives of Neurology & Psychiatry. 25 (2): 299. doi:10.1001/archneurpsyc.1931.02230020085005. ISSN 0096-6754.
  2. ↑ Froukh, Tawfiq (2019). "First Record Mutations in the Genes ASPA and ARSA Causing Leukodystrophy in Jordan". BioMed Research International. 2019: 1–7. doi:10.1155/2019/7235914. ISSN 2314-6133.
  3. ↑ 3.0 3.1 3.2 Matalon, R.; Michals, K.; Sebesta, D.; Deanching, M.; Gashkoff, P.; Casanova, J.; Optiz, John M.; Reynolds, James F. (1988). "Aspartoacylase deficiency and N-acetylaspartic aciduria in patients with canavan disease". American Journal of Medical Genetics. 29 (2): 463–471. doi:10.1002/ajmg.1320290234. ISSN 0148-7299.
  4. ↑ 4.0 4.1 von Jonquieres, Georg; Spencer, Ziggy H. T.; Rowlands, Benjamin D.; Klugmann, Claudia B.; Bongers, Andre; Harasta, Anne E.; Parley, Kristina E.; Cederholm, Jennie; Teahan, Orla; Pickford, Russell; Delerue, Fabien; Ittner, Lars M.; Fröhlich, Dominik; McLean, Catriona A.; Don, Anthony S.; Schneider, Miriam; Housley, Gary D.; Rae, Caroline D.; Klugmann, Matthias (2017). "Uncoupling N-acetylaspartate from brain pathology: implications for Canavan disease gene therapy". Acta Neuropathologica. 135 (1): 95–113. doi:10.1007/s00401-017-1784-9. ISSN 0001-6322.
  5. ↑ 5.0 5.1 5.2 Reddy, Nihaal; Calloni, Sonia F.; Vernon, Hilary J.; Boltshauser, Eugen; Huisman, Thierry A. G. M.; Soares, Bruno P. (2018). "Neuroimaging Findings of Organic Acidemias and Aminoacidopathies". RadioGraphics. 38 (3): 912–931. doi:10.1148/rg.2018170042. ISSN 0271-5333.
  6. ↑ 6.0 6.1 Zayed, Hatem (2015). "Canavan disease: An Arab scenario". Gene. 560 (1): 9–14. doi:10.1016/j.gene.2015.02.009. ISSN 0378-1119.
  7. ↑ Matalon, Reuben; Matalon, Kimberlee Michals (2002). "Canavan disease". Obstetrics and Gynecology Clinics of North America. 29 (2): 297–304. doi:10.1016/S0889-8545(01)00003-1. ISSN 0889-8545.
  8. ↑ Traeger, Eveline C.; Rapin, Isabelle (1998). "The Clinical Course of Canavan Disease". Pediatric Neurology. 18 (3): 207–212. doi:10.1016/S0887-8994(97)00185-9. ISSN 0887-8994.
  9. ↑ Gordon N (2001). "Canavan disease: a review of recent developments". Eur J Paediatr Neurol. 5 (2): 65–9. doi:10.1053/ejpn.2001.0467. PMID 11589315.
  10. ↑ Reddy N, Calloni SF, Vernon HJ, Boltshauser E, Huisman TAGM, Soares BP (2018). "Neuroimaging Findings of Organic Acidemias and Aminoacidopathies". Radiographics. 38 (3): 912–931. doi:10.1148/rg.2018170042. PMID 29757724.
  11. ↑ Hoshino, Hideki; Kubota, Masaya (2014). "Canavan disease: Clinical features and recent advances in research". Pediatrics International. 56 (4): 477–483. doi:10.1111/ped.12422. ISSN 1328-8067.
  12. ↑ Nagabhushan Kalburgi S, Khan NN, Gray SJ (2013). "Recent gene therapy advancements for neurological diseases". Discov Med. 15 (81): 111–9. PMC 5554939. PMID 23449113.
  13. ↑ Assadi, Mitra; Janson, Christopher; Wang, Dah-Jyuu; Goldfarb, Olga; Suri, Neeti; Bilaniuk, Larissa; Leone, Paola (2010). "Lithium citrate reduces excessive intra-cerebral N-acetyl aspartate in Canavan disease". European Journal of Paediatric Neurology. 14 (4): 354–359. doi:10.1016/j.ejpn.2009.11.006. ISSN 1090-3798.
  14. ↑ Janson, Christopher; McPhee, Scott; Bilaniuk, Larissa; Haselgrove, John; Testaiuti, Mark; Freese, Andrew; Wang, Dah-Jyuu; Shera, David; Hurh, Peter; Rupin, Joan; Saslow, Elizabeth; Goldfarb, Olga; Goldberg, Michael; Larijani, Ghassem; Sharrar, William; Liouterman, Larisa; Camp, Angelique; Kolodny, Edwin; Samulski, Jude; Leone, Paola (2002). "Gene Therapy of Canavan Disease: AAV-2 Vector for Neurosurgical Delivery of Aspartoacylase Gene (ASPA) to the Human Brain". Human Gene Therapy. 13 (11): 1391–1412. doi:10.1089/104303402760128612. ISSN 1043-0342.
  15. ↑ Leone, P.; Shera, D.; McPhee, S. W. J.; Francis, J. S.; Kolodny, E. H.; Bilaniuk, L. T.; Wang, D.-J.; Assadi, M.; Goldfarb, O.; Goldman, H. W.; Freese, A.; Young, D.; During, M. J.; Samulski, R. J.; Janson, C. G. (2012). "Long-Term Follow-Up After Gene Therapy for Canavan Disease". Science Translational Medicine. 4 (165): 165ra163–165ra163. doi:10.1126/scitranslmed.3003454. ISSN 1946-6234.

Template:WH Template:WS

Retrieved from "https://www.wikidoc.org/index.php?title=Canavan_disease&oldid=1651186"