Is myopathy with rimmed vacuoles a hallmark of juvenile neuronal ceroid lipofuscinosis (CLN3)?


The neuronal ceroid lipofuscinoses (NCLs) are a clinically and genetically heterogeneous group of severe neurodegenerative diseases characterized by the intracellular accumulation of autofluorescent lipopigment storage material in both neural and peripheral tissues. The clinical course includes progressive dementia, seizures, and progressive visual failure [1]. The NCLs were originally classified into four main forms based on the age of onset: infantile (INCL), late infantile (LINCL), juvenile (JNCL), and adult (ANCL). With the identification of molecular defects, however, the NCLs are now classified numerically according to the underlying gene defect. In fact, CLN3 refers to the JNCL, the most common form of NCL caused by mutations in the CLN3 gene, regardless of the age of onset. JNCL has also been named as Batten disease, Vogt–Spielmeyer disease, and Spielmeyer–Sjogren disease. Classic CLN3 presents at 5–10 years of age, and typically leads to death in the second-to-third decade of life. Currently, there are 67 mutations in CLN3 gene (http:// that are known to cause JNCL, the most common of which is a 1.02-kb deletion occurring in 85 % of patients. This deletion, that removes exons 7 and 8 and the surrounding intronic DNA, leads to a frameshift and premature termination codon that most likely leads to a truncated and non-functional protein. In addition, as previously shown, the premature termination codon induced by the 1.02-kb deletion is recognized by nonsense-mediated decay, leading to CLN3 messenger ribonucleic acid (RNA) degradation and subsequent decrease in protein production [1]. The pathological hallmark of CLN3 is the ultrastructural pattern of lipopigment with a ‘fingerprint’ profile, which can have three different appearances: pure within a lysosomal residual body, in conjunction with curvilinear or rectilinear profiles, and as a small component within large membrane-bound lysosomal vacuoles. The combination of fingerprint profiles within lysosomal vacuoles is a regular feature of blood lymphocytes from patients with CLN3. In our study, we report a patient with the common homozygote deletion (1.02 kb) of the CLN3 gene and a myopathy with autophagic vacuoles. The patient, a 19-year-old woman, was born at term, by Cesarean delivery and after an uneventful pregnancy. Her parents were first cousins. Psychomotor development was normal. Since the age of 8, she presented with progressive cognitive and visual impairment, and speech and gait disorders. She also had multiple brief seizures, characterized by loss of consciousness, lip cyanosis, followed by generalized jerks. At the age of 12, she presented with dementia, epilepsy, retinal dystrophy, and apraxic gait. EEG showed multifocal and diffuse spikes and slow rhythms. Cardiological examination was normal. & Eugenia Borgione

DOI: 10.1007/s10072-015-2439-z

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@article{Borgione2015IsMW, title={Is myopathy with rimmed vacuoles a hallmark of juvenile neuronal ceroid lipofuscinosis (CLN3)?}, author={Eugenia Borgione and Filippa Castello and Mariangela Lo Giudice and Sandro Santa Paola and Simona Salvatore and Gianna Berti and Alessandro Malandrini and Maria Bottitta and Sebastiano Antonino Musumeci and Carmela Scuderi}, journal={Neurological Sciences}, year={2015}, volume={37}, pages={805-807} }