1/19. Use of localized proton nuclear magnetic resonance spectroscopy in Canavan's disease.Canavan's disease is characterized by megalencephaly, leukodystrophy and early motor and mental retardation. On computerized tomography and magnetic resonance imaging, severe changes compatible with white matter disease due to demyelination is observed. It has been demonstrated that urinary N-acetylaspartate levels are increased because of a deficiency of aspartoacylase (N-acyl-L-aspartate aminohydrolase) in these patients. In this study, with the use of proton nuclear magnetic resonance spectroscopy, we were able to demonstrate elevated levels of N-acetylaspartate compared to choline and creatine in the frontal region white matter of three patients. The in vivo measurement of N-acetylaspartate, choline and creatine in the brain by magnetic resonance spectroscopy offers an additional noninvasive diagnostic test for establishing the diagnosis of Canavan's disease.- - - - - - - - - - ranking = 1keywords = white (Clic here for more details about this article) |
2/19. Protracted course of N-acetylaspartic aciduria in two non-Jewish siblings: identical clinical and magnetic resonance imaging findings.canavan disease (CD) or N-acetylaspartic aciduria (NAA) is a severe, progressive, autosomal recessive leukodystrophy, occurring mainly among Ashkenazi Jewish individuals. We report clinical and MRI findings in two, non-Jewish, Greek siblings, 7 and 5 years, respectively, with a protracted form of NAA. The constellation of identical clinical course and identical MRI findings with involvement of the basal ganglia, the brainstem, the dentate nucleus and the subcortical white matter in both siblings, as well as the absence of the three commonest mutations found in both Jewish and non-Jewish CD patients, give support to the existence of a protracted form of NAA with a milder clinical course, presumably genetically determined.- - - - - - - - - - ranking = 0.5keywords = white (Clic here for more details about this article) |
3/19. Van der Knaap's vacuolating leukoencephalopathy: two additional cases.We present two new cases with infantile-onset megalencephaly and a characteristic magnetic resonance imaging (MRI) pattern including severe white-matter abnormalities and subcortical cysts. In one of the patients MRI at the early age of 9 months showed pronounced white matter swelling. In another patient the swelling of white matter was less pronounced at 12 years of age.- - - - - - - - - - ranking = 1.5keywords = white (Clic here for more details about this article) |
4/19. canavan disease: diffusion magnetic resonance imaging findings.A 15-month-old boy with canavan disease is reported in whom a restricted diffusion pattern on diffusion magnetic resonance imaging (MRI) (high signal on b = 1,000 mm2/s images and low apparent diffusion coefficient [ADC] values) was evident in the affected regions of the brain, including the peripheral white matter, globi pallidi, thalami, brainstem, dorsal pons, and dentate nuclei. The ADC values at these regions ranged from 0.42 to 0.56 x 10(-3) mm2/s compared with the normal ADC values from the uninvolved deep frontal white matter (0.68-0.92 x 10(-3) mm2/s). The known histopathologic features in canavan disease include edematous and gelatinous brain tissue associated with diffuse vacuolization. Considering these and the diffusion MRI findings in this patient, it is likely that existence of a gel (gelatinous) state rather than the usual sol state of water molecules in the affected brain regions accounted for the restricted diffusion pattern in canavan disease.- - - - - - - - - - ranking = 1keywords = white (Clic here for more details about this article) |
5/19. Ultrasound findings in follow-up investigations in a case of aspartoacylase deficiency (canavan disease).Aspartoacylase deficiency is a neurodegenerative disease which typically starts in the first months of life with muscular hypotonia and developmental standstill. One of the first diagnostic procedures in this situation is an ultrasound of the brain. There is little information available about sonographic changes in canavan disease. We present for the first time an ultrasound follow-up in a proven case of aspartoacylase deficiency from 3 weeks to 22 months. High echogenicity of the white matter was present in the neonatal period. Additional sonographic phenomena resulting in a characteristic pattern were shown in further investigations. The distinctive sonomorphology is compared to a few other cases in the literature. The correlation to the neuropathological course of the white matter changes is discussed. Recognition of the sonographic features in addition to the clinical presentation may contribute to an effective biochemical work-up.- - - - - - - - - - ranking = 1keywords = white (Clic here for more details about this article) |
6/19. Possible genotype-phenotype correlations in children with mild clinical course of canavan disease.canavan disease is characterised as a rare, neurodegenerative disease that usually causes death in early childhood. It is an autosomal recessive disorder due to an aspartoacylase (ASPA) deficiency. The causative gene has been mapped to chromosome 17 pter-p13. Here we describe three affected children from two Greek families with an unusually mild course of canavan disease. All children presented with muscular hypotonia and macrocephaly. diagnosis was based on elevated N-acetylaspartate in urine, reduced aspartoacylase activity in fibroblasts, and marked white matter changes on cerebral imaging. All three affected individuals exhibited continuous psychomotor development without any regression. Genetic analyses revealed compound heterozygous mutations (Y288 C; F295 S) in two individuals. The Y288 C variant was previously described in a child with macrocephaly, mild developmental delay, increased signal intensity in the basal ganglia, partial cortical blindness and retinitis pigmentosa, and slightly elevated N-acetylaspartate in the urine. Demonstration of the same variant in two unusually mildly affected canavan disease patients and absence of this variant in 154 control chromosomes suggest a possible pathogenic role in mild canavan disease. In the third individual, two homozygous sequence variants were identified, which comprise the known G274R mutation and a novel K213E variant.- - - - - - - - - - ranking = 0.5keywords = white (Clic here for more details about this article) |
7/19. Atypical MRI findings in canavan disease: a patient with a mild course.canavan disease is a severe, progressive leukodystrophy with an autosomal recessive inheritance, caused by aspartoacylase (ASPA) deficiency. The characteristic MRI features include diffuse, symmetrical white matter degeneration in the subcortical areas, with bilateral involvement of the globus pallidus. Proton magnetic resonance spectroscopy of the brain shows an increase in the concentration of N-acetylaspartic acid (NAA). The altered NAA metabolism has been traced to mutations in the gene encoding ASPA, located on chromosome 17 (17p13-ter). We present here a patient with a mild form of canavan disease confirmed with the absent ASPA activity, atypical MRI findings, related to compound heterozygosity for a missense mutation, p.Tyr288Cys, and the known pan-European mutation, the p.Ala305Glu.- - - - - - - - - - ranking = 0.5keywords = white (Clic here for more details about this article) |
8/19. canavan disease: from spongy degeneration to molecular analysis.Establishing the basic defect in canavan disease has led to reliable biochemical methods for the diagnosis of this disease. The isolation of the gene and identification of mutations causing canavan disease have led to the possibility of using dna methods for the diagnosis of canavan disease and for carrier detection. A surprising finding is the high carrier frequency of this gene defect among Ashkenazi Jewish people. Analysis for two mutations leads to the identification of 97% of Jewish patients with canavan disease, and screening of Ashkenazi jews is possible. N-Acetylaspartic acid has been considered to be an inert compound. The pathophysiology of canavan disease links lack of NAA hydrolysis to a severe, debilitating white matter disease. Currently, NAA is being studied in many other brain disorders, such as alzheimer disease, huntington disease, and stroke. However, the only disease with a specific defect in the metabolism of NAA is canavan disease. An animal model for canavan disease is needed to study some of the questions regarding the role of NAA in brain tissue, and for the study of therapeutic modalities, including gene therapy.- - - - - - - - - - ranking = 0.5keywords = white (Clic here for more details about this article) |
9/19. Oculodentodigital dysplasia with cerebral white matter abnormalities in a two-generation family.Oculodentodigital dysplasia (ODDD) is an autosomal dominant disorder involving eye and face abnormalities, syndactyly, and enamel hypoplasia. Some individuals with ODDD also have spastic paraparesis. Previously, we reported on a woman with sporadic ODDD and progressive neurologic dysfunction who had cerebral white matter abnormalities demonstrated by magnetic resonance imaging (MRI). We now describe a 2-generation family with ODDD and progressive paraparesis associated with leukodystrophic changes documented by MRI. This family represents one of the largest pedigrees with ODDD described so far. The presence of abnormal white matter changes in both sporadic and inherited forms of ODDD suggests that the phenotype of ODDD should be expanded to include spastic paraparesis.- - - - - - - - - - ranking = 3keywords = white (Clic here for more details about this article) |
10/19. Deletion of mitochondrial dna in patient with chronic tubulointerstitial nephritis.We report a mitochondrial dna deletion (2.6 kb) in a boy with tubulointerstitial nephritis in whom chronic renal failure and leukodystrophy subsequently developed. Elevated lactate values in plasma and cerebrospinal fluid were suggestive of a defect in the mitochondrial respiratory chain. High amounts of deleted mitochondrial dna were present in muscle and cerebral white matter. On the basis of this observation, we suggest giving consideration to genetic defects of oxidative phosphorylation in any attempt to determine the origin of unexplained chronic tubulointerstitial nephritis, especially when seemingly unrelated organs are involved.- - - - - - - - - - ranking = 0.5keywords = white (Clic here for more details about this article) |
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