Ultrasound Findings in Follow-Up Investigations in a Case of Aspartoacylase Deficiency (Canavan Disease)

doi:10.1055/s-2003-39601

Cited by 7 publications

(4 citation statements)

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“…As demonstrated in previous case reports on CD [11,12], the typical changes of the brain surface with reversal of white and gray matter echogenicity and a highly echogenic pial demarcation (Fig. 5) are well understandable considering the pathophysiology mentioned above.…”

Section: Discussionsupporting

confidence: 64%

“…Nevertheless, US will be applied as first line imaging method in macrocephaly. US features of leukodystrophies are described in few articles about Aicardi-Goutières syndrome (leukodystrophy with calcifications) [23] or even Canavan [10][11][12][13] and Alexander's disease (fibrinoid leukodystrophy) [24], both leukodystrophies with megalencephaly. The hall mark of in US imaging findings in leucodystrophies is white matter hyperechogenicity.…”

Section: Discussionmentioning

confidence: 99%

“…Diagnostic criteria are diffuse leukodystrophy and diffusion restriction in neuroimaging studies [8], elevated acetylaspartic acid in the CSF and urine [2] as well as a NAA peak in MR spectroscopy [9] Concerning ultrasound (US) diagnosis of CD there are only few case reports in the literature from 1986 to 2014 which report white matter hyperechogenicity [10][11][12][13] as well as changes of cerebral surface [11].…”

Section: Introductionmentioning

confidence: 99%

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Canavan’s spongiform leukodystrophy (Aspartoacylase deficiency) with emphasis on sonographic features in infancy: description of a case report and review of the literature

et al. 2022

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Canavan disease (CD; MIM 271,900) or spongy degeneration of the central nervous system (CNS) is a lethal, rare autosomal recessive leukodystrophy, first described in 1931 (Canavan in Arch Neurol Psychiatry 25: 299–308, 1931). The clinical presentation includes severe neurologic impairment and macrocephaly with onset of symptoms at the age of 3–5 months. Biochemical and genetic fundamentals of the disease are elucidated. Imaging diagnosis is principally based on MRI with important role of MR spectroscopy. We report the cerebral sonographic findings in a severely affected infant with CD: Diffuse hyperechogenicity and small multicystic changes of white matter as well as an inverted pattern of echogenicity between cortical gray and subcortical white matter. These findings are compared to to the few cases found in literature and to normal ultrasound examples. Finally, ultrasound and MRI imaging findings are correlated.

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Canavan’s spongiform leukodystrophy (Aspartoacylase deficiency) with emphasis on sonographic features in infancy: description of a case report and review of the literature

et al. 2022

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“…In humans, the CD syndrome is marked by early onset, hydrocephalus, macroencephaly, head-lag, ataxia, blindness, psychomotor retardation, and widespread spongiform myelin sheath vacuolization with progressive demyelination [2][3][4]. In addition to the hydrocephalus and spongiform vacuolization, the global osmotic nature of the disease is also apparent in the swelling of astrocytes, as well as in increased cerebrospinal fluid (CSF) space [5]. Metabolic hallmarks of the disease include a 20-30% elevation in the total of neuron-specific N-acetylaspartate (NAA) and its anabolic product N-acetylaspartylglutamate (NAAG) in brain gray matter (GM) and white matter (WM) [2].…”

Section: Nature Of Canavan Diseasementioning

confidence: 99%

Are Astrocytes the Missing Link Between Lack of Brain Aspartoacylase Activity and the Spongiform Leukodystrophy in Canavan Disease?

Baslow

Guilfoyle

2009

Neurochem Res

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Canavan disease (CD) is a genetic degenerative brain disorder associated with mutations of the gene encoding aspartoacylase (ASPA). In humans, the CD syndrome is marked by early onset, hydrocephalus, macroencephaly, psychomotor retardation, and spongiform myelin sheath vacuolization with progressive leukodystrophy. Metabolic hallmarks of the disease include elevated N-acetylaspartate (NAA) levels in brain, plasma and CSF, along with daily excretion of large amounts of NAA and its anabolic metabolite, N-acetylaspartylglutamate (NAAG). Of the observed neuropathies, the most important appears to be the extensive demyelination that interferes with normal neuronal signaling. However, finding the links between the lacks of ASPA activity in oligodendrocytes, the buildup of NAA in white matter (WM) and the mechanisms underlying the edematous spongiform leukodystrophy have remained elusive. In this analytical review we consider what those links might be and propose that in CD, the pathological buildup of NAA in limited WM extracellular fluid (ECF) is responsible for increased ECF osmotic-hydrostatic pressure and initiation of the demyelination process. We also hypothesize that NAA is not directly liberated by neurons in WM as it is in gray matter, and that its source in WM ECF is solely as a product of the catabolism of axon-released NAAG at nodes of Ranvier by astrocyte NAAG peptidase after it has docked with the astrocyte surface metabotropic glutamate receptor 3. This hypothesis ascribes for the first time a possible key role played by astrocytes in CD, linking the lack of ASPA activity in myelinating oligodendrocytes, the pathological buildup of NAA in WM ECF, and the spongiform demyelination process. It also offers new perspectives on the cause of the leukodystrophy in CD, and on possible treatment strategies for this inherited metabolic disease.

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Canavan disease: A white matter disorder

Kumar

Mattan

Vellis

2006

Ment. Retard. Dev. Disabil. Res. Rev.

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Breakdown of oligodendrocyte-neuron interactions in white matter (WM), such as the loss of myelin, results in axonal dysfunction and hence a disruption of information processing between brain regions. The major feature of leukodystrophies is the lack of proper myelin formation during early development or the onset of myelin loss late in life. These early childhood WM diseases are described as hypomyelination or dysmyelination arising from a primary block in normal myelin synthesis because of a genetic mutation expressed in oligodendrocytes, or failure in myelination secondary to neuronal or astroglial dysfunctions (van der Knaap 2001 Dev. Med. Child Neurol. 43:705-712). Here, we describe the pathophysiological parameters of Canavan disease (CD), caused by genetic mutations of the aspartoacylase (ASPA) gene, a metabolic enzyme restricted in the central nervous system (CNS) to oligodendrocytes. CD presents pathophysiological dysfunctions similar to diseases caused by myelin gene mutations, such as Pelizaeus-Merzbacher disease (PMD) and several animal models, such as myelin deficient rat (md), jimpy (jp), shiverer (sh), and quaking (qk viable) mutant mice. These single gene mutations have pleiotropic effects, whereby the alteration of one myelin gene expression disrupts functional expression of other oligodendrocyte genes with an outcome of hypomyelination/dysmyelination. Among all of the known leukodystrophies, CD is the first disorder, which was approved and tested for the adeno-associated virus vector (AAV)-ASPA gene therapy (Leone et al. 2000 Ann. Neurol. 48:27-38; Janson et al. 2001 Trends Neurosci. 24:706-712) without much success following the first two attempts. ASPA gene delivery attempts in animal models have shown a lowering of N-acetyl L-aspartate and a change in motor functions, while sponginess of the WM, a characteristic of CD remained unchanged (Matalon et al. 2003 Mol. Ther. 7 (5, Part 1):580-587; McPhee et al. 2005 Brain Res. Mol. Brain Res. 135:112-121) even with better viral serotype and delivery of the gene during early phase of development (Klugmann et al. 2005 Mol. Ther. 11:745-753). While different approaches are being sought for the success of gene therapy, there are pivotal developmental questions to address regarding the specific regions of the CNS and cell lineages that become the target for the onset and progression of CD symptoms from early to late stages of development.

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Ultrasound Findings in Follow-Up Investigations in a Case of Aspartoacylase Deficiency (Canavan Disease)

Cited by 7 publications

References 7 publications

Canavan’s spongiform leukodystrophy (Aspartoacylase deficiency) with emphasis on sonographic features in infancy: description of a case report and review of the literature

Canavan’s spongiform leukodystrophy (Aspartoacylase deficiency) with emphasis on sonographic features in infancy: description of a case report and review of the literature

Are Astrocytes the Missing Link Between Lack of Brain Aspartoacylase Activity and the Spongiform Leukodystrophy in Canavan Disease?

Canavan disease: A white matter disorder

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