Agradecimentos: This study was supported by Fundo de Incentivo à Pesquisa e Eventos (FIPE/HCPA-15-0281) and Instituto Nacional de Genética Médica Populacional (INaGeMP), CNPq 465549/2014-4, CAPES 88887.136366/2017-00, FAPERGS 17/2551.0000521.0. CONFLICT OF INTEREST Luciana Giugliani, Carlos Eduardo Steiner, Chong Ae Kim, Charles Marques Lourenço, Mara Lucia Schmitz Ferreira Santos, Carolina Fischinger Moura de Souza, Ana Carolina Brusius-Facchin, Guilherme Baldo, Mariluce Riege, Roberto Giugliani declare that they have no conflict of interest. Funding information Fundo de Incentivo à Pesquisa e Eventos, Grant/Award Number: 15-0281; and Instituto Nacional de Genética Médica Populacional (INaGeMP), Grant/Award Numbers: FAPERGS 17/2551.0000521.0, CAPES 88887.136366/2017-00, CNPq 465549/2014-4 Ver menos

Abstract: GM1 gangliosidosis is a lysosomal storage disorder caused by ß-galactosidase deficiency. To date, prospective studies for GM1 gangliosidosis are not available, and only a few have focused on the adult form. This retrospective cross-sectional study focused on clinical findings in Brazilian patients with the adult form of GM1 gangliosidosis collected over 2?years. Ten subjects were included in the study. Eight were males and two females, with median age at diagnosis of 11.5 years (IQR, 4-34?years). Short stature and weight below normal were seen in five out of the six patients with data available. Radiological findings revealed that the most frequent skeletal abnormalities were beaked vertebrae, followed by hip dysplasia, and platyspondyly. Neurological examination revealed that dystonia and swallowing problems were the most frequently reported. None of the patients presented hyperkinesia, truncal hypertonia, Parkinsonism, or spinal cord compression. Clinical evaluation revealed impairment in activities of cognitive/intellectual development and behavioral/psychiatric disorders in all nine subjects with data available. Language/speech impairment (dysarthria) was found in 8/9 patients, fine motor and gross motor impairments were reported in 7/9 and 5/9 patients, respectively. Impairment of cognition and daily life activities were seen in 7/9 individuals. Our findings failed to clearly identify typical early or late alterations presented in GM1 gangliosidosis patients, which confirms that it is a very heterogeneous condition with wide phenotypic variability. This should be taken into account in the evaluation of future therapies for this challenging condition Ver menos