Spongy degeneration of the brain, Canavan disease: Biochemical and molecular findings

Reuben Matalon, Kimberlee Michals-Matalon

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Canavan disease is a severe progressive leukodystrophy characterized by swelling and spongy degeneration of the white matter of the brain. It is an autosomal recessive disease found more frequently among Ashkenazi Jews. The clinical features are those of severe mental retardation with inability to gain developmental milestones. Hypotonia, head lag and macrocephaly are characteristic of Canavan disease and become apparent after 5-6 months of age. Massive excretion in the urine of N-acetylaspartic acid is the biochemical marker for Canavan disease, which is caused by deficiency of the enzyme aspartocylase. This discovery allowed for accurate diagnosis of Canavan disease, while prior to that, a brain biopsy was needed. The gene for aspartoacylase has been cloned and two mutations predominate among Ashkenazi Jewish individuals with Canavan disease and account for more than 98% of the Ashkenazi Jewish patients. The mutations among other ethnic groups are more diverse. The carrier frequency for the two common mutations among Ashkenazi Jews was found to be surprisingly high, 1: 37. Screening for carriers is now common practice for this population. A knock-out mouse for Canavan disease is being genetically engineered in our laboratory. The mouse model will allow for development of strategies for gene therapy.

Original languageEnglish (US)
Pages (from-to)471-481
Number of pages11
JournalFetal and Pediatric Pathology
Volume18
Issue number6
DOIs
StatePublished - 1998

Fingerprint

Canavan Disease
Brain Diseases
Jews
Mutation
Megalencephaly
Muscle Hypotonia
Brain
Ethnic Groups
Knockout Mice
Intellectual Disability
Genetic Therapy
Biomarkers
Head
Urine
Biopsy
Enzymes

Keywords

  • aspartoacylase
  • Canavan disease
  • macrocephaly
  • N-acetylaspartic acid
  • review
  • spongy degeneration of the brain

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Pediatrics, Perinatology, and Child Health

Cite this

Spongy degeneration of the brain, Canavan disease : Biochemical and molecular findings. / Matalon, Reuben; Michals-Matalon, Kimberlee.

In: Fetal and Pediatric Pathology, Vol. 18, No. 6, 1998, p. 471-481.

Research output: Contribution to journalArticle

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