Canavan disease
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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
History and Symptoms
- Most commonly patients usually present at three to six months of age with lethargy, weak cry, poor head control, macrocephaly, blindness, hypotonia, poor feeding due to dysfunctional swallowing, seizures, and/or irritability.[7]
- The most common form of the disease is also the most serious form and progresses rapidly.
- 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.
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
MRI
Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Surgery
Primary Prevention
Secondary Prevention
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 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.