| 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. ( info) |
2/30. 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. ( info) |
3/30. 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. ( info) |
4/30. Novel splice site mutation of aspartoacylase gene in a Turkish patient with canavan disease. canavan disease is a severe, progressive autosomal recessive neurodegenerative leukodystrophy. canavan disease occurs more frequently among Ashkenazi Jewish individuals with two predominant mutations in the aspartoacylase (ASPA) gene. The disease is less frequent in non-Jewish individuals and the mutations randomly reside on the ASPA gene, with one mutation seen more frequently among patients of European extraction. In the present study we report a novel homozygous donor splice site mutation of intron 4 in a child with first-cousin parents of Turkish extraction. ( info) |
5/30. Upper airway abnormalities in canavan disease. OBJECTIVE: To describe upper airway anatomical abnormalities associated with canavan disease. methods: Retrospective case report. RESULTS: physical examination and laryngoscopy demonstrated oropharyngeal narrowing, macroglossia, and bronchial asymmetry in a child with canavan disease. tracheostomy decreased problems with chronic aspiration and obstructive sleep apnea. CONCLUSIONS: Oropharyngeal obstruction and bronchial asymmetry are previously undescribed upper airway abnormalities found in an individual with canavan disease. tracheostomy is an effective method of managing chronic aspiration and obstruction in these patients. ( info) |
| 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. ( info) |
7/30. Canavan's leukodystrophy is associated with defects in cochlear neurodevelopment and deafness. The authors present the temporal bone histopathology of two siblings (4 months old and 6 months old at autopsy) with Canavan's disease, an autosomal recessive leukodystrophy that is variably associated with sensorineural hearing loss. The histopathology demonstrated bilateral absence of the organ of corti throughout the apical and basal cochlea and mild secondary atrophy of the spiral ganglia neurons. The vestibular end organs and ganglia were normal. These findings implicate a role of aminoacylase II in the neurodevelopment of the organ of corti. ( info) |
8/30. 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. ( info) |
9/30. A fatal case of spongiform leukoencephalopathy linked to "chasing the dragon". BACKGROUND: "Chasing the dragon" involves placing heroin on aluminum foil, heating it from below with a flame, and inhaling the pyrolysate through a straw. It has rarely been associated with the development of a progressive spongiform leukoencephalopathy. CASE REPORT: A 43-year-old woman presented with 2 weeks of bizarre behavior, forgetfulness, and slowed speech and movements. serum, cerebrospinal fluid, and head computed tomography (CT) scan were normal. The patient progressed to coma and expired during week 4 of hospital admission. The family confirmed that she "chased the dragon." cause of death at post mortem examination was spongiform leukoencephalopathy. CONCLUSION: The diagnosis of heroin pyrolysate-induced spongiform leukoencephalopathy should be considered in a patient with a history of "chasing the dragon" and neurobehavioral changes, including confusion, apathy, cerebellar signs, and motor restlessness. ( info) |
10/30. Mild elevation of N-acetylaspartic acid and macrocephaly: diagnostic problem. 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. ( info) |