Canavan disease: Difference between revisions
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===Medical Therapy=== | ===Medical Therapy=== | ||
*There is no treatment for Canavan disease; the mainstay of therapy is supportive care: | *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. | |||
** | ** | ||
Revision as of 15:42, 14 August 2020
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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
For patient information, click here
| Canavan disease | |
| ICD-9 | 330.0 |
|---|---|
| OMIM | 271900 |
| DiseasesDB | 29780 |
| MedlinePlus | 001586 |
Overview
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
- Canavan disease is a rare inherited disorder following an autosomal recessive pattern of inheritance. [3]
- It is caused by a deficiency of enzyme aspartoacylase.
- Aspartoacylase is responsible for breakdown of N-acetyl aspartate (NAA) into aspartic acid and acetate.
- Decreased level of aspartoacylase results in accumulation of N-acetyl aspartate (NAA) in the brain causing abnormal myelination and progressive cerebral spongy degeneration.[3]
Causes
- This autosomal recessive disease is caused by mutation in ASPA gene on short arm of chromosome 17 responsible for aspartoacylase enzyme production.[4]
- Canavan disease must be differentiated from other dysmylinating diseases that affect the white matter such as:
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.
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
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 dosease have relentless progression and soon is complicated by blindness, spasticity, decerebrate posturing and eventual death.[7]
- 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
- An elevated concentration of urinary N-acetyl aspartate (NAA) aids in the diagnosis of Canavan disease.[5]
- 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.[3]
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
- 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. [8]
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
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.[9]
Other Diagnostic Studies
- There are no other diagnostic studies associated with Canavan disease.
Treatment
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.
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.
See also
External links
- Information on the disorder from the National Institute of Neurological Disorder and Stroke
- Cell & Gene Therapy Center at UMDNJ
- Beat Canavan Disease - A web site dedicated to raising funds to save a Canavan baby's life
- Canavan Research Illinois - A public charity devoted to curing Canavan disease
- Canavan Research - A foundation devoted to curing Canavan disease
- Jacob's Cure - A non-profit organization dedicated to raising money for Canavan disease research
References
- ↑ 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.
- ↑ 3.0 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.
- ↑ 4.0 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.
- ↑ 5.0 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.
- ↑ 6.0 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.