Electron miscroscopic and enzyme histochemical studies of the cerebellum in spongy degeneration

Adachi, Masazumi; Torii, J; Schneck, Larry; Volk, Bruno W.

doi:10.1007/bf00687899

Cited by 54 publications

(17 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[1][2][3][4] Cytosine arabinoside has been given to children who developed secondary parkinsonism, but the drug was not implicated as the cause of the parkinsonism, which was attributed to amphotericin and cyclophosphamide in previous reports. Toxins are a much more common cause of adult secondary parkinsonism than of pediatric parkinsonism.…”

Section: Discussionmentioning

confidence: 99%

Mild Elevation of N-Acetylaspartic Acid and Macrocephaly: Diagnostic Problem

et al. 2003

View full text Add to dashboard Cite

Patients with slightly increased excretion of N-acetylaspartic acid in urine, together with macrocephaly, present a dignostic dilemma for Canavan's disease. We describe a 13-year-old male patient with macrocephaly, mild developmental delay, increased signal intensity in the basal ganglia bilaterally, partial cortical blindness, and retinitis pigmentosa. Although the clinical course and magnetic resonance imaging findings did not resemble typical Canavan's disease, N-acetylaspartic acid excretion in the patient's urine was slightly elevated, 99.90 +/- 4.00 microg/mg creatinine, whereas the normal control range was < 83 microg/mg creatinine. Cultured skin fibroblasts from the patient showed no aspartoacylase activity. Cloning of genomic DNA isolated from the patient's fibroblasts showed an intronic mutation, specifically deletion of -2A and -3C at the acceptor site of exon 3 and disrupting the normal splicing of the gene. A second mutation was found in exon 6, 863 A-->G in aspartoacylase complementary DNA, causing a tyrosine-to-cysteine (Y288C) amino acid substitution. Expression of the mutation on exon 6 showed normal aspartoacylase activity. These data suggest that expression of the mutation may help to understand the enzyme defect in a patient with slightly increased N-acetylaspartic acid excretion.

show abstract

Section: Discussionmentioning

confidence: 99%

Mild Elevation of N-Acetylaspartic Acid and Macrocephaly: Diagnostic Problem

et al. 2003

View full text Add to dashboard Cite

show abstract

“…Canavan disease (CD) is an autosomal recessive leukodystrophy with clinical symptoms, including megalencephaly, hypotonia, and mental retardation (Adachi et al, 1972(Adachi et al, , 1973Adornato et al, 1972;Canavan, 193 1;van-Bogaert and Bertrand, 1967). The basic biochemical defect is the deficiency of enzyme aspartoacylase (ASPA) (Matalon et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

Novel (cys152>arg) missense mutation in an Arab patient with Canavan disease

et al. 1995

View full text Add to dashboard Cite

“…The histopathology of the brain in Canavan disease is striking, with spongy degeneration of the myelin fibre, astrocytic swelling and elongated mitochondria. In spite of these specific findings there have been reports suggesting that similar spongy degeneration may occur in other diseases, although the electron microscopy of Canavan disease is considered to be rather specific (Adachi et al 1972;Adornato et al 1972). Since the basic defect for Canavan disease was not known, the most widely accepted idea for the spongy degeneration was disturbance in the cell ion pump that leads to oedema and sponginess (O'Brien et al 1985).…”

mentioning

confidence: 99%

Canavan disease: Biochemical and molecular studies

Matalon

Kaul

Michals

1993

J of Inher Metab Disea

View full text Add to dashboard Cite

Deficiency of the enzyme aspartoacylase and the accumulation of N-acetylaspartic acid lead to a severe leukodystrophy and spongy degeneration of the brain, Canavan disease (McKusick 271900). Since our discovery in 1988 of the defect in Canavan disease, 144 patients with Canavan disease have been diagnosed in our laboratory. Most of these children are of Ashkenazi Jewish extraction. The level of enzyme activity can be used for carrier testing. Prenatal diagnosis has been difficult using the enzyme assay owing to the low activity of aspartoacylase in cultured chorionic villus samples or amniocytes. The determination of N-acetylaspartic acid in the amniotic fluid is another parameter for diagnosis; however, the levels may not always be elevated. Bovine and human aspartoacylase have been purified in our laboratory. Bovine and human cDNA and genomic clones have been isolated and six exons have been localized. This information is being used for the study of Canavan disease at the molecular level.

show abstract

Electron miscroscopic and enzyme histochemical studies of the cerebellum in spongy degeneration

Cited by 54 publications

References 19 publications

Mild Elevation of N-Acetylaspartic Acid and Macrocephaly: Diagnostic Problem

Mild Elevation of N-Acetylaspartic Acid and Macrocephaly: Diagnostic Problem

Novel (cys152>arg) missense mutation in an Arab patient with Canavan disease

Canavan disease: Biochemical and molecular studies

Contact Info

Product

Resources

About