Late-onset Tay–Sachs disease: Adverse effects of medications and implications for treatment

Shapiro, Barbara E.; Hatters‐Friedman, Susan; Fernandes-Filho, José; Anthony, Kyle; Natowicz, Marvin R.

doi:10.1212/01.wnl.0000233847.72349.b6

Cited by 20 publications

(9 citation statements)

References 6 publications

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“…Late‐onset Tay‐Sachs disease (LOTS) is an autosomal recessive lysosomal storage disease due to compound heterozygous or homozygous mutations in HEXA . These lead to decreased Beta‐hexosaminidase A activity and subsequent intracellular accumulation of CNS gangliosides . Patients may present in childhood, adolescence, or early adulthood.…”

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confidence: 99%

Atypical presentation of late‐onset Tay‐sachs disease

Deik

Saunders‐Pullman

2014

Muscle and Nerve

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Introduction Late-onset Tay-Sachs disease (LOTS) is a lysosomal storage disease caused by deficient Beta-hexosaminidase A activity. Methods We describe a 53-year-old woman who presented with adult-onset leg weakness, and whose initial diagnosis was progressive muscular atrophy without identifiable etiology. Development of cerebellar ataxia in mid-life prompted reassessment. Results Beta-hexosaminidase A quantification assay demonstrated absence of the isozyme. Genetic testing identified compound heterozygous mutations in the HEXA gene, confirming the diagnosis of LOTS. Conclusions The phenotypic spectrum of LOTS includes motor neuronopathy, ataxia, choreoathetosis, neuropathy, and psychiatric symptoms in various combinations. This patient highlights the emergence of different clinical features over many years and emphasizes the need to consider LOTS in the differential diagnosis of progressive muscular atrophy.

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confidence: 99%

Atypical presentation of late‐onset Tay‐sachs disease

Deik

Saunders‐Pullman

2014

Muscle and Nerve

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“…Also a late diagnosis may delay proper genetic counseling regarding disease progression and reproductive risks, which is especially important in Ashkenazi Jewish patients because the disease is transmitted in autosomal recessive fashion. (2,13) In patients showing signs of lower motor neuron involvement, cerebellar and pyramidal signs and marked cerebellar atrophy the late-onset TSD should be suspected, and the first step in establishing the diagnosis should be to determine the serum activity of HexA.…”

Section: Discussionmentioning

confidence: 99%

Late Onset Tay-Sachs Disease in a Non-Jewish Patient: Case Report

Maier

Bajkó

Moţăţăianu

et al. 2017

Acta Medica Marisiensis

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Tay-Sachs disease (TSD) is a rare, inherited, autosomal rececessive lysosomal storage disease. The late-onset form is an uncommon condition among non-Jewish population. We present the case of a 32 years old male patient without Jewish origins, in whom the disease began in adolescence and was initially diagnosed with spinal muscular atrophy. He developed progressively protean neurological symptomatology, including tetraparesis, cerebellar and extrapyramidal syndromes. The diagnosis was based on the cerebral MRI, showing severe cerebellar atrophy and the determination of the Hexosaminidase A activity, revealing low level. In patients showing signs of lower motor neuron involvement, cerebellar and pyramidal signs and marked cerebellar atrophy the late-onset TSD should be suspected, and the first step in establishing the diagnosis should be to determine the serum activity of Hexosaminidase A.

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“…In some autosomal recessive metabolic diseases, medications may worsen symptoms. For example, in Tay-Sachs disease, treatment with risperidone, haloperidol, and chlorpromazine may precipitate neurological worsening and should be avoided (Shapiro et al 2006). This effect is postulated to result from reduction in residual lysosomal function.…”

Section: Discussionmentioning

confidence: 99%

Cognitive and Antipsychotic Medication Use in Monoallelic GBA-Related Parkinson Disease

et al. 2014

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Mutations in glucosidase, beta, acid (GBA) are associated with cognitive impairment in Parkinson disease (PD) as well as dementia with Lewy bodies. For both of these diseases, dementia and hallucinations are typically treated with cholinesterase inhibitors and antipsychotics. However, in some lysosomal storage disorders certain antipsychotic medications are poorly tolerated. This study examined cholinesterase inhibitor and antipsychotic use in monoallelic GBA-related PD to explore potential pharmacogenetic relationships. Monoallelic GBA mutation carriers with PD (GBA-PD) with at least two clinic visits (n ¼ 34) were matched for age-of-onset and gender to GBA and leucine-rich repeat kinase 2 (LRRK2) mutation negative idiopathic PD subjects (IPD) (n ¼ 60). Information regarding cholinesterase inhibitor and antipsychotic use as well as impaired cognition (UPDRS Mentation >1) and hallucinations (UPDRS Thought Disorder >1) were obtained. GBA-PD more frequently reported hallucinations (HR ¼ 5.0; p ¼ 0.01) and they were more likely to have cognitive impairment but this was not statistically significant (HR 2.2, p ¼ 0.07). Antipsychotic use was not significantly different between GBA-PD and IPD (HR ¼ 1.9; p ¼ 0.28), but GBA-PD were more likely to have sustained cholinesterase inhibitor use (HR ¼ 3.1; p ¼ 0.008), even after adjustment for cognition and hallucinations. Consistent with reports of worse cognition, GBA-PD patients are more likely to use cholinesterase inhibitors compared to IPD. While there was no difference in antipsychotic use between IPD and GBA-PD, persistent use of quetiapine in GBA-PD suggests that it is tolerated and that a significant interaction is unlikely. Further prospective study in larger samples with more extensive cognitive assessment is warranted to better understand pharmacogenetic relationships in GBA-PD.

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Late-onset Tay–Sachs disease: Adverse effects of medications and implications for treatment

Cited by 20 publications

References 6 publications

Atypical presentation of late‐onset Tay‐sachs disease

Atypical presentation of late‐onset Tay‐sachs disease

Late Onset Tay-Sachs Disease in a Non-Jewish Patient: Case Report

Cognitive and Antipsychotic Medication Use in Monoallelic GBA-Related Parkinson Disease

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