Achalasia in a Patient with Adult-Onset Tay-Sachs Disease

Nathanson, Jeffrey W.; Winans, Charles S.

doi:10.1007/s10620-006-3097-z

Cited by 2 publications

(2 citation statements)

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“…Late‐onset Tay‐Sachs disease (LOTS) is a rare autosomal‐recessive genetic disorder caused by insufficient activity of the lysosomal enzyme, beta‐hexosaminidase A, resulting in intracellular accumulation of gangliosides in the central nervous system. Clinical manifestations reported in the literature include ataxia, unsteadiness of gait, poor coordination, muscle weakness, difficulty climbing stairs, tremor, extrapyramidal signs (parkinsonism), pyramidal tract signs, dystonia, dysphagia, achalasia, dysarthria, stutter, saccades, ocular motor disturbances, motor neuron disease, cognitive dysfunction, intellectual impairment, psychiatric disturbance, psychosis, bipolar disorder, depression, and anxiety, all in the absence of a fundoscopic cherry‐red spot (observed in infantile Tay‐Sachs) . Imaging findings reported in the literature include cerebellar atrophy, cerebral atrophy, and hypodensity in the thalamus …”

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confidence: 99%

Dysarthria and Stutter as Presenting Symptoms of Late‐Onset Tay‐Sachs Disease in Three Siblings

Grim

Phillips

Renner

2015

Movement Disord Clin Pract

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Late-onset Tay-Sachs disease (LOTS) is a rare autosomal-recessive genetic disorder caused by insufficient activity of the lysosomal enzyme, beta-hexosaminidase A, resulting in intracellular accumulation of gangliosides in the central nervous system. Clinical manifestations can include unsteadiness in gait, muscle weakness, cognitive dysfunction, psychiatric disturbance, and dysarthric speech. The variable presentation of these symptoms, combined with the late onset of the disease, often results in misdiagnosis. We present video of 3 sibling cases of LOTS in which a dysarthric stutter was the sole presenting symptom in order to better characterize the phenotype of this disease.Late-onset Tay-Sachs disease (LOTS) is a rare autosomal-recessive genetic disorder caused by insufficient activity of the lysosomal enzyme, beta-hexosaminidase A, resulting in intracellular accumulation of gangliosides in the central nervous system. Clinical manifestations reported in the literature include ataxia, unsteadiness of gait, poor coordination, muscle weakness, difficulty climbing stairs, tremor, extrapyramidal signs (parkinsonism), pyramidal tract signs, dystonia, dysphagia, achalasia, dysarthria, stutter, saccades, ocular motor disturbances, motor neuron disease, cognitive dysfunction, intellectual impairment, psychiatric disturbance, psychosis, bipolar disorder, depression, and anxiety, all in the absence of a fundoscopic cherry-red spot (observed in infantile Tay-Sachs). [1][2][3][4][5][6][7][8] Imaging findings reported in the literature include cerebellar atrophy, cerebral atrophy, and hypodensity in the thalamus. 2,3,[5][6][7] The variable presentation of LOTS patients, combined with onset of symptoms in adolescence or adulthood, often contributes to misdiagnosis. In addition, video of the clinical presentation of a LOTS patient has never been presented in a medical journal. We present video of 3 sibling cases of LOTS in which a dysarthric stutter was the sole presenting symptom in order to better characterize the phenotype of this disease. Cases Case 1This 42-year-old female, born to nonconsanguineous parents of non-Jewish European background, first developed a stutter at approximately age 10. She participated in speech therapy at that time with no improvement. At age 22, the patient was evaluated for recurrent paroxysms of encephalopathy after an episode of psychosis. On exam, she exhibited symptoms of mild cognitive impairment, but had no cortical findings of aphasia, apraxia, agnosia, or neglect. The remainder of her neurological exam revealed bilateral Babinski signs, mild ataxia, and staccato dysarthria. Subsequent diagnostic testing revealed significantly decreased hexosaminidase A levels with normal total hexosaminidase, consistent with a diagnosis of LOTS. Brain MRI brain revealed mild cerebellar atrophy. Case 2This 45-year-old female, the older sister of the patient described in case 1, developed a stutter at age 8. In her early twenties, she was diagnosed with bipolar affective disorder and was hospital...

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confidence: 99%

Dysarthria and Stutter as Presenting Symptoms of Late‐Onset Tay‐Sachs Disease in Three Siblings

Grim

Phillips

Renner

2015

Movement Disord Clin Pract

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“…The mean age at disease onset was 21 years (±10, 10–54), 19 years old (±7, 10–42) for the TS patients and 27 years old (±14, 10–54) for the SD patients (Table ) . Eight of the 17 (47%) patients with SD had an onset after 25 years old versus 5 of 40 (12.5%) patients with TS.…”

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confidence: 98%

Natural History of Adult Patients with GM2 Gangliosidosis

Masingue

Dufour

Lenglet

et al. 2020

Annals of Neurology

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Objective GM2 gangliosidoses are lysosomal diseases due to biallelic mutations in the HEXA (Tay–Sachs disease [TS]) or HEXB (Sandhoff disease [SD]) genes, with subsequent low hexosaminidase(s) activity. Most patients have childhood onset, but some experience the first symptoms during adolescence/adulthood. This study aims to clarify the natural history of adult patients with GM2 gangliosidosis. Methods We retrospectively described 12 patients from a French cohort and 45 patients from the literature. Results We observed 4 typical presentations: (1) lower motoneuron disorder responsible for proximal lower limb weakness that subsequently expanded to the upper limbs, (2) cerebellar ataxia, (3) psychosis and/or severe mood disorder (only in the TS patients), and (4) a complex phenotype mixing the above 3 manifestations. The psoas was the first and most affected muscle in the lower limbs, whereas the triceps and interosseous were predominantly involved in the upper limbs. A longitudinal study of compound motor action potentials showed a progressive decrease in all nerves, with different kinetics. Sensory potentials were sometimes abnormally low, mainly in the SD patients. The main brain magnetic resonance imaging feature was cerebellar atrophy, even in patients without cerebellar symptoms. The prognosis was mainly related to gait disorder, as we showed that beyond 20 years of disease evolution, half of the patients were wheelchair users. Interpretation Improved knowledge of GM2 gangliosidosis in adults will help clinicians achieve correct diagnoses and better inform patients on the evolution and prognosis. It may also contribute to defining proper outcome measures when testing emerging therapies. ANN NEUROL 2020;87:609–617

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Achalasia in a Patient with Adult-Onset Tay-Sachs Disease

Cited by 2 publications

References 29 publications

Dysarthria and Stutter as Presenting Symptoms of Late‐Onset Tay‐Sachs Disease in Three Siblings

Dysarthria and Stutter as Presenting Symptoms of Late‐Onset Tay‐Sachs Disease in Three Siblings

Natural History of Adult Patients with GM2 Gangliosidosis

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