Giugliani Luciana, Steiner Carlos Eduardo, Kim Chong Ae, Lourenço Charles Marques, Santos Mara Lucia Schmitz Ferreira, de Souza Carolina Fischinger Moura, Brusius-Facchin Ana Carolina, Baldo Guilherme, Riegel Mariluce, Giugliani Roberto
National Institute of Population Medical Genetics (INAGEMP) Porto Alegre Brazil.
Department of Medical Genetics Faculdade de Medicina, UNICAMP Campinas Brazil.
JIMD Rep. 2019 Jul 17;49(1):96-106. doi: 10.1002/jmd2.12067. eCollection 2019 Sep.
GM1 gangliosidosis is a lysosomal storage disorder caused by β-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.
GM1神经节苷脂贮积症是一种由β-半乳糖苷酶缺乏引起的溶酶体贮积病。迄今为止，尚无针对GM1神经节苷脂贮积症的前瞻性研究，仅有少数研究关注成人型。这项回顾性横断面研究聚焦于在两年内收集的巴西成人型GM1神经节苷脂贮积症患者的临床发现。该研究纳入了10名受试者。其中8名男性，2名女性，诊断时的中位年龄为11.5岁（四分位间距，4 - 34岁）。在有数据的6名患者中，5名患者出现身材矮小和体重低于正常水平。影像学检查结果显示，最常见的骨骼异常是鸟嘴样椎体，其次是髋关节发育不良和平椎。神经学检查显示，肌张力障碍和吞咽问题是最常报告的症状。所有患者均未出现运动亢进、躯干张力亢进、帕金森综合征或脊髓受压。临床评估显示，在有数据的所有9名受试者中，认知/智力发育活动和行为/精神障碍均有受损。8/9的患者存在语言/言语障碍（构音障碍），7/9和5/9的患者分别报告有精细运动和粗大运动障碍。7/9的个体存在认知和日常生活活动受损。我们的研究结果未能明确识别出GM1神经节苷脂贮积症患者典型的早期或晚期改变，这证实了它是一种具有广泛表型变异性的高度异质性疾病。在评估针对这种具有挑战性疾病的未来治疗方法时应考虑到这一点。
