La dystrophie spongieuse hereditaire des enfants (Canavan: Van Bogaert-Bertrand)

Mirimanoff, Patrick

doi:10.1016/0022-510x(76)90101-5

Cited by 11 publications

(3 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, an earlier brain tissue histology report of a 4-year-old CD patient described an increased density of OLs (Mirimanoff, 1976), and yet another report described loss of OLs (Adachi et al, 1966). These reports were based on staining tissues with various dyes.…”

Section: Discussionmentioning

confidence: 93%

Lack of aspartoacylase activity disrupts survival and differentiation of neural progenitors and oligodendrocytes in a mouse model of Canavan disease

Kumar

Biancotti

Matalon

et al. 2009

J of Neuroscience Research

View full text Add to dashboard Cite

Loss of the oligodendrocyte (OL)-specific enzyme aspartoacylase (ASPA) from gene mutation results in the sponginess and loss of white matter (WM) in Canavan disease (CD). This study addresses the fate of OLs during the pathophysiology of CD in an adult ASPA knockout (KO) mouse strain. Massive arrays of neural stem/progenitor cells, immunopositive for PSA-NCAM, nestin, vimentin, and NG2, were observed within the severely affected spongy WM of the KO mouse brain. In these mice, G1-->S cell cycle progression was confirmed by an increase in cdk2-kinase activity, a reduction in mitotic inhibitors p21(Cip1) and p27(Kip1), and an increase in bromodeoxyuridine (BrdU) incorporation. Highly acetylated nuclear histones H2B and H3 were detected in adult KO mouse WM, suggesting the existence of noncompact chromatin as seen during early development. Costaining for BrdU- or Ki67-positive cells with markers for neural progenitors confirmed a continuous generation of OL lineage cells in KO WM. We observed a severe reduction in 21.5- and 18.5-kDa myelin basic protein and PLP/DM20 proteolipid proteins combined with a decrease in myelinated fibers and a perinuclear retention of myelin protein staining, indicating impairment in protein trafficking. Death of OLs, neurons, and astrocytes was identified in every region of the KO brain. Immature OLs constituted the largest population of dying cells, particularly in WM. We also report an early expression of full-length ASPA mRNA in normal mouse brain at embryonic day 12.5, when OL progenitors first appear during development. These findings support involvement of ASPA in CNS development and function.

show abstract

Section: Discussionmentioning

confidence: 93%

Lack of aspartoacylase activity disrupts survival and differentiation of neural progenitors and oligodendrocytes in a mouse model of Canavan disease

Kumar

Biancotti

Matalon

et al. 2009

J of Neuroscience Research

View full text Add to dashboard Cite

show abstract

“…CD is diagnosed by detection of elevated NAA in urine or blood or in brain by proton MR spectroscopy [ 3 ], as well as by ASPA mutation analysis [ 4 ]. Histologically the disease is characterized by insufficient myelination and progressive spongy degeneration of the brain white matter [ 5 , 6 ]. The perinatal period is often uneventful and subtle changes during early infancy may escape attention.…”

Section: Introductionmentioning

confidence: 99%

The natural history of Canavan disease: 23 new cases and comparison with patients from literature

Bley

Denecke

Kohlschütter

et al. 2021

Orphanet J Rare Dis

View full text Add to dashboard Cite

Background Canavan disease (CD, MIM # 271900) is a rare and devastating leukodystrophy of early childhood. To identify clinical features that could serve as endpoints for treatment trials, the clinical course of CD was studied retrospectively and prospectively in 23 CD patients. Results were compared with data of CD patients reported in three prior large series. Kaplan Meier survival analysis including log rank test was performed for pooled data of 82 CD patients (study cohort and literature patients). Results Onset of symptoms was between 0 and 6 months. Psychomotor development of patients was limited to abilities that are usually gained within the first year of life. Macrocephaly became apparent between 4 and 18 months of age. Seizure frequency was highest towards the end of the first decade. Ethnic background was more diverse than in studies previously reported. A CD severity score with assessment of 11 symptoms and abilities was developed. Conclusions Early hallmarks of CD are severe psychomotor disability and macrocephaly that develop within the first 18 months of life. While rare in the first year of life, seizures increase in frequency over time in most patients. CD occurs more frequently outside Ashkenazi Jewish communities than previously reported. Concordance of phenotypes between siblings but not patients with identical ASPA mutations suggest the influence of yet unknown modifiers. A CD severity score may allow for assessment of CD disease severity both retrospectively and prospectively.

show abstract

“…Canavan leukodystrophy, a recessively inherited CNS disease of infancy and childhood caused by ASPA (EC 3.5.1.15) loss-of-function mutations, 1,2 is characterized clinically by progressive impairment of cognitive and motor function and pathologically by forebrain, cerebellar, and brainstem myelin intraperiod line splitting and astroglial vacuolation ("spongiform leukodystrophy"). [3][4][5][6] ASPA encodes aspartoacylase, an oligodendrocyte-enriched enzyme that cleaves N-acetyl-L-aspartate (NAA) to L-aspartate and acetate. 7 The lack of aspartoacylase in Canavan disease results in a substantial elevation in the brain concentration of NAA ([NAA B ]).…”

Section: Introductionmentioning

confidence: 99%

Brain Nat8l Knockdown Suppresses Spongiform Leukodystrophy in an Aspartoacylase-Deficient Canavan Disease Mouse Model

et al. 2018

View full text Add to dashboard Cite

Canavan disease, a leukodystrophy caused by loss-of-function ASPA mutations, is characterized by brain dysmyelination, vacuolation, and astrogliosis ("spongiform leukodystrophy"). ASPA encodes aspartoacylase, an oligodendroglial enzyme that cleaves the abundant brain amino acid N-acetyl-L-aspartate (NAA) to L-aspartate and acetate. Aspartoacylase deficiency results in a 50% or greater elevation in brain NAA concentration ([NAA]). Prior studies showed that homozygous constitutive knockout of Nat8l, the gene encoding the neuronal NAA synthesizing enzyme N-acetyltransferase 8-like, prevents aspartoacylase-deficient mice from developing spongiform leukodystrophy. We now report that brain Nat8l knockdown elicited by intracerebroventricular/intracisternal administration of an adeno-associated viral vector carrying a short hairpin Nat8l inhibitory RNA to neonatal aspartoacylase-deficient Aspa mice lowers [NAA] and suppresses development of spongiform leukodystrophy.

show abstract

La dystrophie spongieuse hereditaire des enfants (Canavan: Van Bogaert-Bertrand)

Cited by 11 publications

References 53 publications

Lack of aspartoacylase activity disrupts survival and differentiation of neural progenitors and oligodendrocytes in a mouse model of Canavan disease

Lack of aspartoacylase activity disrupts survival and differentiation of neural progenitors and oligodendrocytes in a mouse model of Canavan disease

The natural history of Canavan disease: 23 new cases and comparison with patients from literature

Brain Nat8l Knockdown Suppresses Spongiform Leukodystrophy in an Aspartoacylase-Deficient Canavan Disease Mouse Model

Contact Info

Product

Resources

About