Magnetic resonance imaging in juvenile Canavan disease

Abstract

We present a 2-year-old boy and a 6-year-old girl with mild Canavan disease (CD). Aspartoacylase activity in skin fibroblasts was deficient. Magnetic resonance imaging (MRI) of the brain did not show the prominent leucodystrophy previously reported in CD, but there was a hyperintense signal from the lentiform nuclei and the heads of the caudate nuclei on the T2-weighted MR images. This suggests a specific vulnerability of the corpus striatum in these patients. In the older patient, the white matter became affected at the age of 6 years. Proton magnetic resonance spectroscopy (1H-MRS) of white matter revealed a normal concentration of N-acetyl-L-aspartate (NAA) and a markedly decreased concentration of choline containing compounds (Cho) in the boy but a normal ratio of NAA to Cho in the girl. We conclude that deficient NAA catabolism affects myelin metabolism. This may present as changes in the striatum and/or as a low concentration of Cho before leucodystrophy appears on MRI.

Quantitative measurements with localized 1H MR spectroscopy in children with Canavan's disease

“…In these cases, it was found that there was only a strong decrease in the choline-containing compounds, while the NAA concentration with respect to the volume (21) or the wet weight of brain tissue (9) remained constant.…”

Mild‐onset presentation of Canavan's disease associated with novel G212A point mutation in aspartoacylase gene

“…Toft and colleagues 9 reported two patients with double mutations in C914A (A305E) which had a mild clinical presentation; the subjects could walk by age 20 months with normal gross motor control, muscle tone, and vision. Like most Canavan's disease patients, they were macrocephalic and had a significant history of seizures.…”

“…4,5 Studies before the identification of the ASPA gene suggested that milder or protracted phenotypes of Canavan's disease may exist. 1,6,9 However, it is now recognized that protracted cases in which patients survive through adolescence or adulthood are more likely to be a function of aggressive supportive care and earlier diagnosis due to improved clinical screening (ie, lead time bias) rather than genetic differences affecting the natural history of disease, 7 and the grading of infantile, early, or juvenile variants of Canavan's disease is flawed. 8 Nevertheless, rare reports have described an atypical, relatively indolent course of Canavan's disease which may have a variable genetic component.…”

“…8 Nevertheless, rare reports have described an atypical, relatively indolent course of Canavan's disease which may have a variable genetic component. Mildly symptomatic patients reported by Toft and colleagues 9 were determined to be homozygous for C914A. 10 In addition, a protracted, relatively mild clinical course was reported in two non-Jewish siblings 11 without any of the known gene mutations, for which a genetic identification was not made initially.…”

Redirecting N-acetylaspartate metabolism in the central nervous system normalizes myelination and rescues Canavan disease

“…Later, children develop spasticity, ataxia, and seizure. Most CD patients die within the first years of life, although some live to adolescence or adulthood (9)(10)(11)(12). Neuropathology reveals the formation of vacuoles and loss of myelin structures throughout the CNS, particularly in deep brain regions such as the thalamus, brain stem, and cerebellum (13,14).…”