Canavan disease is a neurodegenerative disorder characterized by progressive nerve cell damage in the brain. The severity of the disorder can vary, ranging from mild developmental delay to intellectual disability and lack of motor development. There are two forms of Canavan disease categorized by the severity and age of onset: 1. Neonatal/infantile form This is the severe and most common form of Canavan disease. Infants with this form appear normal at birth, but signs and symptoms gradually progress in early infancy (3-5 months). Typical symptoms include macrocephaly (abnormally large heads), poor head control, hypotonia (weak muscle tone) and delayed speech and motor skills. Some may develop paralysis, blindness, hearing loss or seizures. Life expectancy for individuals with this form of the disease is variable, with some surviving only into childhood and others surviving until adolescence or beyond. 2. Mild/juvenile form This form is less common with disease onset in childhood. Individuals affected with this form have mild developmental delays in speech and motor skills. Life expectancy is typically normal. Canavan disease is caused by mutations in the ASPA gene. This gene is responsible for making the protein aspartoacylase, which helps to break down N-acetyl-L-aspartic acid (NAA) in the brain. Mutations in the ASPA gene reduce or eliminate the function of aspartoacylase. Without this protein, NAA cannot be broken down properly, resulting in accumulation of NAA in the brain. Excessive NAA interferes with the formation of myelin sheaths resulting in the progressive breakdown of existing myelin. This leads to progressive damage and degeneration of the brain due to malfunctioning nerves which lace the myelin protective covering. References: Birken DL and Oldendorf WH (1989). N-Acetyl-L-Aspartic acid: A literature review of a compound prominent in 1H-NMR spectroscopic studies of brain. Neuroscience & Biobehavioral Reviews. 13(1): 23–31. Jose CP, Ferreira MD, Schreiber-Agus N, Carter SM, Klugman S, MDa, Gregg AR, Gross SJ (2014). Carrier testing for Ashkenazi Jewish disorders in the prenatal setting: navigating the genetic maze. American Journal of Obstetrics and Gynecology. 211(3): 197-204. Matalon R, Michals-Matalon K (1999)
[Updated 2011 Aug 11]. Canavan Disease. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016. Olsen TR, Tranebjærg L, Kvittingen EA, Hagenfeldt L, Møller C, Nilssen O (2002). Two novel aspartoacylase gene (ASPA) missense mutations specific to Norwegian and Swedish patients with Canavan disease. J Med Genet 39(9): e55