Metabolic Brain Disease

, Volume 31, Issue 2, pp 475–479 | Cite as

Atypical clinical and radiological course of a patient with Canavan disease

  • Catherine Sarret
  • Odile Boespflug-Tanguy
  • Diana Rodriguez
Short Communication


Canavan disease (CD) is a rare metabolic disorder caused by aspartoacylase (ASPA) deficiency. It leads to severe neurological degeneration with spongiform brain degeneration. Accumulation of N-acetylaspartate (NAA) in brain and urine is specific to the disease and guides diagnosis. Magnetic resonance imaging (MRI) usually shows diffuse white matter abnormalities with involvement of the basal ganglia. Mild forms of the disease with a more favorable clinical course and radiological involvement of the basal ganglia without white matter abnormalities have also been reported. Here we report an atypical case of a girl aged nine years with CD. The disease started at the classical age of five months. Classical elevation of NAA in brain and urine was present and genetic analysis identified mutations in the ASPA gene. However, clinical evolution was milder than typical CD, with partial motor impairment and relatively well-preserved cognitive skills. MRI was also atypical with low white matter involvement and unusual topography and evolution of abnormalities in the basal ganglia.


Canavan disease Aspartoacylase N-acetyl-aspartate Magnetic resonance imaging 1H magnetic resonance spectroscopy 


Compliance with ethical standards

Conflict of interest

Authors declare that they have no conflict of interest.

Informed consent

All the procedures followed complied with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards”. Informed consent was obtained from the patient’s family before inclusion in the study.


  1. Baslow MH, Guilfoyle DN (2013) Canavan disease, a rare early-onset human spongiform leukodystrophy: insights into its genesis and possible clinical interventions. Biochimie 95:946–956CrossRefPubMedGoogle Scholar
  2. Elpeleg ON, Shaag A (1999) The spectrum of mutations of the aspartoacylase gene in Canavan disease in non-Jewish patients. J Inherit Metab Dis 22:531–534CrossRefPubMedGoogle Scholar
  3. Francis JS, Markov V, Leone P (2014) Dietary triheptanoin rescues oligodendrocyte loss, dysmyelination and motor function in the nur7 mouse model of Canavan disease. J Inherit Metab Dis 37:369–381CrossRefPubMedGoogle Scholar
  4. Guo F, Bannerman P, Mills Ko E, et al. (2015) Ablating N-acetylaspartate prevents leukodystrophy in a Canavan disease model. Ann Neurol 77:884–888CrossRefPubMedGoogle Scholar
  5. Hershfield JR, Pattabiraman N, Madhavarao CN, Namboodiri MA (2007) Mutational analysis of aspartoacylase: implications for Canavan disease. Brain Res 1148:1–14CrossRefPubMedPubMedCentralGoogle Scholar
  6. Hoshino H, Kubota M (2014) Canavan disease: clinical features and recent advances in research. Pediatr Int 56:477–483CrossRefPubMedGoogle Scholar
  7. Janson CG, Kolodny EH, Zeng BJ, et al. (2006) Mild-onset presentation of Canavan’s disease associated with novel G212A point mutation in aspartoacylase gene. Ann Neurol 59:428–431CrossRefPubMedGoogle Scholar
  8. Madhavarao CN, Arun P, Moffett JR, et al. (2005) Defective N-acetylaspartate catabolism reduces brain acetate levels and myelin lipid synthesis in Canavan’s disease. Proc Natl Acad Sci U S A 102:5221–5226CrossRefPubMedPubMedCentralGoogle Scholar
  9. Matalon R, Michals-Matalon K (1999) Canavan Disease. In: Pagon RA, Adam MP, Ardinger HH, et al. (eds) GeneReviews (internet), Seattle, pp. 1993–2015 (updated 2011)Google Scholar
  10. Michals K, Matalon R (2011) Canavan disease. In: Raymond GV, Eichler F, Fatemi A, Naidu S, Leukodystrophies (eds) London, Mac Keith Press, 2:156–69Google Scholar
  11. Michel SJ, Given CA (2006) Case 99: Canavan disease. Radiology 241:310–314CrossRefPubMedGoogle Scholar
  12. Nave KA, Trapp BD (2008) Axon-glial signaling and the glial support of axon function. Annu Rev Neurosci 31:535–561CrossRefPubMedGoogle Scholar
  13. Nguyen HV, Ishak GE (2015) Canavan disease - unusual imaging features in a child with mild clinical presentation. Pediatr Radiol 45:457–460CrossRefPubMedGoogle Scholar
  14. Toft PB, Geiss-Holtorff R, Rolland MO, et al. (1993) Magnetic resonance imaging in juvenile Canavan disease. Eur J Pediatr 152:750–753CrossRefPubMedGoogle Scholar
  15. Velinov M, Zellers N, Styles J, Wisniewski K (2008) Homozygosity for mutation G212A of the gene for aspartoacylase is associated with atypical form of Canavan’s disease. Clin Genet 73:288–289CrossRefPubMedGoogle Scholar
  16. Wittsack HJ, Kugel H, Roth B, Heindel W (1996) Quantitative measurements with localized 1 H MR spectroscopy in children with Canavan’s disease. J Magn Reson Imaging 6:889–893CrossRefPubMedGoogle Scholar
  17. Yalcinkaya C, Benbir G, Salomons GS et al (2005) Atypical MRI findings in Canavan disease: a patient with a mild course. Neuropediatrics 36:336–339.Google Scholar
  18. Zafeiriou DI, Kleijer WJ, Maroupoulos G, et al. (1999) Protracted course of N-acetylaspartic aciduria in two non-Jewish siblings: identical clinical and magnetic resonance imaging findings. Brain Dev 21:205–208CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Catherine Sarret
    • 1
    • 2
  • Odile Boespflug-Tanguy
    • 3
    • 4
  • Diana Rodriguez
    • 4
    • 5
    • 6
  1. 1.Image-Guided Clinical Neuroscience and Connectomics (IGCNC), EA7282University of Auvergne, Clermont-Ferrand University HospitalClermont-FerrandFrance
  2. 2.Department of PediatricsClermont-Ferrand University HospitalClermont-FerrandFrance
  3. 3.APHP, Department of Child Neurology and Metabolic Diseases, Leukodystrophies Reference CentreRobert Debré HospitalParisFrance
  4. 4.Inserm U1141 Paris Diderot Sorbonne University – Paris Cité, DHU PROTECT, Robert Debré HospitalParisFrance
  5. 5.APHP, Department of Child NeurologyArmand Trousseau HospitalParisFrance
  6. 6.Sorbonne Universités, UPMC Univ Paris 06ParisFrance

Personalised recommendations