Katherine E Delaney1, Stephen F Kralik2, Bryan E Hainline3, Meredith R Golomb4. 1. Division of Pediatric Neurology, Department of Neurology, Indiana University School of Medicine and Riley Hospital for Children at Indiana University Health, Indianapolis, Indiana. 2. Division of Pediatric Neuroradiology, Department of Radiology, Indiana University School of Medicine and Riley Hospital for Children at Indiana University Health, Indianapolis, Indiana. 3. Department of Medical and Molecular Genetics, Indiana University School of Medicine and Riley Hospital for Children at Indiana University Health, Indianapolis, Indiana. 4. Division of Pediatric Neurology, Department of Neurology, Indiana University School of Medicine and Riley Hospital for Children at Indiana University Health, Indianapolis, Indiana. Electronic address: mgolomb@iupui.edu.
Abstract
BACKGROUND: Canavan disease is an autosomal recessive leukodystrophy caused by a deficiency of aspartoacylase. The disease has a severe course, with death occurring in the first few years of life. Atypical patients with mild courses have been reported, but acute presentations similar to stroke have not been well described. PATIENT DESCRIPTION: We present a boy who presented at 4 months of age with seizures after an episode of cardiopulmonary arrest is discussed. RESULTS: He was initially thought to have an ischemic watershed stroke based on his initial clinical presentation and magnetic resonance imaging. However, biochemical and follow-up radiologic evaluation were consistent with mild Canavan disease. DNA sequencing of the ASPA gene indicated one known mutation (A305E) and a novel mutation, L30V. Follow-up magnetic resonance imaging did not reveal the atrophy which would have been expected with watershed ischemia. Magnetic resonance spectroscopy demonstrated elevated N-acetyl aspartate to creatinine and N-acetyl aspartate to choline ratios. At 4 years of age, he was normocephalic, with mild clumsiness, speech delay, and seizures. CONCLUSIONS: This child's unusual acute presentation, along with his prolonged mild course, raises questions about the relationship between biochemical signs of abnormal aspartoacylase function and clinical findings. This patient highlights the need for long-term clinical follow-up of children with mild Canavan disease to clarify the significance of these biochemical abnormalities.
BACKGROUND:Canavan disease is an autosomal recessive leukodystrophy caused by a deficiency of aspartoacylase. The disease has a severe course, with death occurring in the first few years of life. Atypical patients with mild courses have been reported, but acute presentations similar to stroke have not been well described. PATIENT DESCRIPTION: We present a boy who presented at 4 months of age with seizures after an episode of cardiopulmonary arrest is discussed. RESULTS: He was initially thought to have an ischemic watershed stroke based on his initial clinical presentation and magnetic resonance imaging. However, biochemical and follow-up radiologic evaluation were consistent with mild Canavan disease. DNA sequencing of the ASPA gene indicated one known mutation (A305E) and a novel mutation, L30V. Follow-up magnetic resonance imaging did not reveal the atrophy which would have been expected with watershed ischemia. Magnetic resonance spectroscopy demonstrated elevated N-acetyl aspartate to creatinine and N-acetyl aspartate to choline ratios. At 4 years of age, he was normocephalic, with mild clumsiness, speech delay, and seizures. CONCLUSIONS: This child's unusual acute presentation, along with his prolonged mild course, raises questions about the relationship between biochemical signs of abnormal aspartoacylase function and clinical findings. This patient highlights the need for long-term clinical follow-up of children with mild Canavan disease to clarify the significance of these biochemical abnormalities.
Authors: V K Kimiskidis; Vasileios Papaliagkas; S Papagiannopoulos; D Zafeiriou; D Kazis; E Tsatsali-Foroglou; Z Kouvatsou; V Kapina; D Koutsonikolas; G Anogianakis; T Geroukis; S Bostantjopoulou Journal: Metab Brain Dis Date: 2017-01-28 Impact factor: 3.584