Abstract
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.
Highlights
Gangliosidoses are autosomal recessive inherited metabolic diseases in which accumulation of gangliosides in the central nervous system (CNS) leads to severe and progressive neurological impairment.[1,2] GM1 gangliosidosis is a lysosomal storage disorder caused by β-galactosidase deficiency
This study aimed to contribute to the better understanding of the adult form of GM1 gangliosidosis, presenting a retrospective characterization of a sample of Brazilian patients by focusing on clinical features
The study was approved by the Ethics Research Committee of Hospital de Clínicas de Porto Alegre (HCPA), followed the Declaration of Helsinki, and the standards established by the authors' Institutional Review Board and granting agency
Summary
Gangliosidoses are autosomal recessive inherited metabolic diseases in which accumulation of gangliosides (glycosphingolipids containing one or more sialic acid residues) in the central nervous system (CNS) leads to severe and progressive neurological impairment.[1,2] GM1 gangliosidosis is a lysosomal storage disorder caused by β-galactosidase deficiency. Primary β-galactosidase deficiency is found in patients with Morquio disease type B (mucopolysaccharidosis IVB; MPS IVB) In this condition, the genetic mutation affects the catalytic activity related to the substrate keratan sulfate, causing a disease marked by bone dysplasia usually without neurological involvement.[3]. The adult form or chronic late-onset variant (type III) has a less severe phenotype, with onset usually between 3 and 30 years, cases with earlier onset and protracted course may occur. It is characterized by progressive neurological impairment, with cerebellar dysfunction, dystonia, slurred speech, and mild vertebral deformities.[2,5]. This study aimed to contribute to the better understanding of the adult form of GM1 gangliosidosis, presenting a retrospective characterization of a sample of Brazilian patients by focusing on clinical features
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