Abstract
BackgroundThe GM2 gangliosidoses (GM2), Tay-Sachs and Sandhoff diseases, are rare, autosomal recessive genetic disorders caused by mutations in the lysosomal enzyme β-hexosaminidase A (HEXA) or β-hexosaminidase B (HEXB) genes, respectively. A minority of patients have a late-onset form of disease that presents from late-childhood to adulthood and has a slowly progressive course with prolonged survival.Little research has been published documenting patient experiences with late-onset Tay-Sachs and Sandhoff diseases and how the disease impacts their daily lives and functioning. This study explored the most frequent symptoms and functional impacts experienced by patients with late-onset GM2 gangliosidosis through interviews with patients and caregivers.MethodsA qualitative research study design was employed, using three focus groups and 18 one-on-one interviews with patients who were recruited at the National Tay-Sachs and Allied Diseases Annual Family Conference. Transcripts were generated from the discussions, and patient quotes were analyzed using a content analysis approach. Concepts were aggregated into symptom and functional impacts, and the frequency of mention in the focus groups and individual interviews was calculated.Key findingsMany of the frequently described symptoms [muscle weakness (n = 19, 95%), “clumsy” gait (n = 12, 60%), fatigue (n = 10, 50%)] and impacts [difficulty walking (n = 19, 95%), falling (n = 17, 85%), and climbing stairs (n = 16, 80%)] disclosed by patients and caregivers were similar to those previously reported in the literature. However, less frequently described symptoms such as gastrointestinal issues (n = 4, 20%) and coughing fits (n = 5, 25%) have been expanded upon. This study evaluated the immediate impact of these symptoms on the patients’ lives to highlight the burden of these symptoms and the functional limitations on daily living activities, independence, and emotional well-being. The findings were used to develop a conceptual disease model that could serve as a foundation for patient-centered outcomes in clinical trials and provide insights to the medical community that may benefit patient care.ConclusionsThis study contributes to the current understanding of symptoms associated with late-onset GM2 gangliosidosis, and further identifies the many consequences and impacts of the disease. These symptoms and impacts could be measured in clinical trials to examine the effects of novel treatments from the patient perspective.
Highlights
The GM2 gangliosidoses (GM2), Tay-Sachs and Sandhoff diseases, are rare, autosomal recessive genetic disorders caused by mutations in the lysosomal enzyme β-hexosaminidase A (HEXA) or β-hexosaminidase B (HEXB) genes, respectively
The GM2 gangliosidoses, Tay-Sachs disease and Sandhoff disease, are virtually clinically indistinguishable autosomal recessive lysosomal storage disorders caused by mutations in the genes encoding the α subunit (HEXA) or β subunit (HEXB), respectively, of the two β-hexosaminidase isoenzymes, hexosaminidase A and hexosaminidase B
Tay-Sachs disease is caused by a deficiency of βhexosaminidase A activity, whereas Sandhoff disease results from a combined deficiency of β-hexosaminidase A and B activities
Summary
The GM2 gangliosidoses (GM2), Tay-Sachs and Sandhoff diseases, are rare, autosomal recessive genetic disorders caused by mutations in the lysosomal enzyme β-hexosaminidase A (HEXA) or β-hexosaminidase B (HEXB) genes, respectively. Little research has been published documenting patient experiences with late-onset Tay-Sachs and Sandhoff diseases and how the disease impacts their daily lives and functioning. The GM2 gangliosidoses, Tay-Sachs disease and Sandhoff disease, are virtually clinically indistinguishable autosomal recessive lysosomal storage disorders caused by mutations in the genes encoding the α subunit (HEXA) or β subunit (HEXB), respectively, of the two β-hexosaminidase isoenzymes, hexosaminidase A (αβ) and hexosaminidase B (ββ). Symptoms of late-onset Tay-Sachs disease include ataxia, dysarthria, muscle weakness, tremors, atrophy, and psychosis [4]. Patients with late-onset Sandhoff disease manifest similar symptoms, including spinocerebellar ataxia, motor deterioration, sensorimotor neuropathy, tremor, dystonia, and psychosis [5]. The age and rate of progression on symptoms vary, but do not significantly affect longevity
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