Canavan Disease, Mutation Analysis, ASPA
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Canavan disease is a severe leukodystrophy resulting from a deficiency of the enzyme aspartoacylase. Mutations in the ASPA gene cause the clinical manifestations of Canavan disease. The deficiency of aspartoacylase leads to spongy degeneration of the brain, and the disease is characterized by delayed development beginning at age 3 to 6 months, head lag, macrocephaly, and hypotonia. Death usually occurs within the first decade of life.
The carrier rate in the Ashkenazi Jewish population is 1/41. Four ASPA mutations are included in this test: 433(-2)A->G, A305E, E285A, and Y231X. The E285A and Y231X mutations account for approximately 98% of the mutations in the Ashkenazi Jewish population. The A305E mutation accounts for approximately 50% of the mutations in the non-Ashkenazi Jewish population.
Carrier testing for individuals of Ashkenazi Jewish ancestry
Prenatal diagnosis in at-risk pregnancies
Confirmation of a suspected clinical diagnosis of Canavan disease in individuals of Ashkenazi Jewish ancestry
An interpretative report will be provided.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This assay will not detect all of the mutations that cause Canavan disease. Therefore, the absence of a detectable mutation does not rule out the possibility that an individual is a carrier of or affected with this disease.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.
Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.
In rare cases, DNA alterations of undetermined significance may be identified.
A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Gross SJ, Pletcher BA, Monaghan KG: Carrier screening individuals of Ashkenazi Jewish descent. Genet Med 2008;10(1):54-56
2. ACOG Committee on Genetics: ACOG Committee Opinion No. 442: Preconception and prenatal carrier screening for genetic diseases in individuals of Eastern European Jewish descent. Obstet Gynecol 2009;Oct;114(4):950-953
3. Matalon R: Canavan disease: diagnosis and molecular analysis. Genet Testing 1997;1:21-25