Article on Tay-Sachs Disease

2021 ◽  
pp. 475-478
Author(s):  
Bhawana. B. Bhende
Keyword(s):  
Autosomal Recessive ◽  
Genetic Disorder ◽  
Single Gene ◽  
Genetic Defect ◽  
Premature Death ◽  
Nerve Cells ◽  
Tay Sachs Disease ◽  
Hexosaminidase A ◽  
Physical Abilities ◽  
The Brain

Tay–Sachs disease is a genetic disorder that results in the destruction of nerve cells in the brain and spinal cord..also known as GM2 gangliosidosis or Hexosaminidase A deficiency) is an autosomal recessive genetic disorder. In its most common variant known as infantile Tay-Sachs disease it presents with a relentless deterioration of mental and physical abilities which commences at 6 months of age and usually results in death by the age of four.It is caused by a genetic defect in a single gene with one defective copy of that gene inherited from each parent. The disease occurs when harmful quantities of gangliosides accumulate in the nerve cells of the brain, eventually leading to the premature death of those cells. There is currently no cure or treatment. Tay- Sachs disease is a rare disease. Other autosomal disorders such as cystic fibrosis and sickle cell anemia are far more common. TSD is an autosomal recessive genetic disorder, meaning that when both parents are carriers, there is a 25% risk of giving birth to an affected child.

Tay-Sachs Disease: Two Novel Rare HEXA Mutations from Pakistan and Morocco

2021 ◽  
Author(s):  
Farah Bibi ◽  
Asmat Ullah ◽  
Thomas Bourinaris ◽  
Stephanie Efthymiou ◽  
Yamna Kriouile ◽  
...  
Keyword(s):  
Genetic Disorder ◽  
Cost Effective ◽  
Genome Project ◽  
Causative Gene ◽  
Tay Sachs Disease ◽  
Clinical Investigations ◽  
Whole Exome ◽  
Hexosaminidase A ◽  
Pakistani Origin ◽  
Targeted Gene Sequencing

Abstract Background Tay-Sachs disease (TSD) is a rare autosomalrecessive genetic disorder characterized by progressive destruction of nerve cells in the brain and spinal cord. It is caused by genetic variations in the HEXA gene leading to a deficiency of β hexosaminidase A (HEXA) isoenzyme activity. This study aimed to identify causative gene variants in 3 unrelated consanguineous families presented with TSD from Pakistan and Morocco. Methods Detailed clinical investigations were carried out on probands in 3 unrelated consanguineous families of Pakistani and Moroccan origin. Targeted gene sequencing and Whole Exome Sequencing (WES) were performed for variant identification. Candidate variants were checked for co-segregation with the phenotype using Sanger sequencing. Public databases including ExAC, GnomAD, dbSNP and the 1,000 Genome Project were searched to determine frequencies of the alleles. Conservation of the missense variants was ensured by aligning orthologous protein sequences from diverse vertebrate species. Results We report on 3 children presented with Tay-Sachs Disease. The β hexosaminidaseA enzyme activity was reduced in the Pakistani patient in one of the pedigrees. Genetic testing revealed 2 novel homozygous variants (p.Asp386Alafs*13 and p.Trp266Gly) in the gene HEXA in Pakistani and Moroccan patients respectively.The third family of Pakistani origin revealed a previously reported variant (p.Tyr427Ilefs*5) in HEXA. p.Tyr427Ilefs*5 is the most commonly occurring pathogenic variationin Ashkenazi but was not reported in Pakistani population. Conclusion Our study further expands the ethnic and mutational spectrum of Tay-Sachs disease emphasizing the usefulness of WES as a powerful diagnostic tool where enzymatic activity is not performed for Tay-Sachs disease. The study recommends targeted screening for these mutations (p.Tyr427Ilefs5) for cost effective testing of TSD patients. Further, the study would assist in carrier testing and prenatal diagnosis of the affected families.

scholarly journals Tay-Sachs disease

2019 ◽  
Vol 67 (3) ◽  
pp. 323-329
Author(s):  
Carlos Andrés Gualdrón-Frías ◽  
Laura Tatiana Calderón-Nossa
Keyword(s):  
Autosomal Recessive ◽  
Neurodegenerative Disorder ◽  
Clinical Manifestations ◽  
Lysosomal Storage ◽  
Adequate Treatment ◽  
Autosomal Recessive Disorders ◽  
Tay Sachs Disease ◽  
Mesh Terms ◽  
Hexosaminidase A ◽  
Gm2 Gangliosidoses

Introduction: Lysosomal storage disease is caused by the deficiency of a single hydrolase (lysosomal enzymes). GM2 gangliosidoses are autosomal recessive disorders caused by deficiency of β-hexosaminidase and Tay-Sachs disease (TSD) is one of its three forms.Objective: To perform a review of the state of the art on TSD describing its definition, epidemiology, etiology, physiopathology, clinical manifestations and news in diagnosis and treatment.Materials and methods: A literature search was carried out in PubMed using the MeSH terms “Tay-Sachs Disease”.Results: 1 233 results were retrieved in total, of which 53 articles were selected. TSD is caused by the deficiency of the lysosomal enzyme β-hexosaminidase A (HexA), and is characterized by neurodevelopmental regression, hypotonia, hyperacusis and cherry-red spots in the macula. Research on molecular pathogenesis and the development of possible treatments has been limited, consequently there is no treatment established to date.Conclusion: TSD is an autosomal recessive neurodegenerative disorder. Death usually occurs before the age of five. More research and studies on this type of gangliosidosis are needed in order to find an adequate treatment.

Unusual thermolability properties of leukocyte beta-hexosaminidase: implications in screening for carriers of Tay-Sachs disease

1993 ◽  
Vol 39 (9) ◽  
pp. 1811-1814 ◽  
Author(s):  
E M Prence ◽  
M R Natowicz ◽  
I Zalewski
Keyword(s):  
Autosomal Recessive ◽  
Sandhoff Disease ◽  
Carrier Testing ◽  
Heat Inactivation ◽  
Reciprocal Relation ◽  
Specific Substrate ◽  
Critical Determinant ◽  
Tay Sachs Disease ◽  
Hexosaminidase A ◽  
Sample Amount

Abstract Tay-Sachs disease (TSD), an autosomal recessive neurodegenerative condition, is the result of a deficiency of beta-hexosaminidase A (hex A). Heterozygotic individuals are screened by analysis for hex A and hex B activities; the percent of hex A is the critical determinant of carrier vs noncarrier status. Most laboratories use a heat-inactivation assay that exploits the differential thermolability of the isoenzymes. However, we have found a reciprocal relation between the apparent leukocyte hex A activity and the amount of the sample used in the assay; i.e., a significant increase in the percent of hex A activity with decreasing amounts of sample. Three sets of data indicate that this phenomenon was caused by an effect on the hex B isoenzyme and not on hex A. This variation in hex A activity with sample amount was not observed when a hex A-specific substrate was used. This phenomenon was also not seen in assays of leukocytes from carriers for Sandhoff disease, a condition associated with a reduction in the amount of hex B. Finally, when leukocytes from a TSD homozygote, containing almost no hex A, were analyzed, marked increases in the percent of hex A were observed with decreasing sample concentrations. These data indicate that misdiagnoses could result from variations in sample concentrations used for TSD carrier testing and support the view that the leukocyte concentrations used for these assays should be standardized.

scholarly journals Tay-Sachs Disease: A Rare Storage Disorder in Children

2021 ◽  
Vol 11 (7) ◽  
pp. 194-196
Author(s):  
Sunil Kumar Agarwalla ◽  
Laxmipriya Tudu ◽  
Arpita Jalan
Keyword(s):  
Lysosomal Storage Disorder ◽  
Autosomal Recessive ◽  
Marked Decrease ◽  
Lysosomal Storage ◽  
Enzyme Replacement ◽  
Developmental Regression ◽  
Tay Sachs Disease ◽  
Hexosaminidase A ◽  
Cherry Red Spot ◽  
Storage Disorder

Tay-Sachs disease is an autosomal recessive lysosomal storage disorder cause by deficiency of enzyme Beta Hexosaminidase A and leading to accumulation of GM2 gangliosides mainly in CNS, results in progressive loss of neurological functions. We report a case of 14 month old male child presented to us with neuro-developmental regression, convulsions and bilateral cherry red spot on funduscopy. The diagnosis of Tay-Sachs disease was made by marked decrease level of enzyme Hexosaminidase A. Key words: Lysosomal storage disorder, GM2 gangliosides, neuro- regression, cherry red spot, Enzyme replacement therapy.

scholarly journals Unusual case of Juvenile Tay-Sachs disease

2019 ◽  
Vol 12 (9) ◽  
pp. e230140
Author(s):  
Huma A Cheema ◽  
Nadia Waheed ◽  
Anjum Saeed
Keyword(s):  
Autosomal Recessive ◽  
Unusual Case ◽  
Neurodegenerative Disorder ◽  
Sphingolipid Metabolism ◽  
Tay Sachs Disease ◽  
First Case ◽  
Hexosaminidase A ◽  
Cherry Red Spot ◽  
Autosomal Recessive Manner

Tay-Sachs disease (TSD) is a type 1 gangliosidosis (GM2) and caused by hexosaminidase A deficiency resulting in abnormal sphingolipid metabolism and deposition of precursors in different organs. It is a progressive neurodegenerative disorder transmitted in an autosomal-recessive manner. There is an accumulation of GM2 in neurocytes and retinal ganglions which result in progressive loss of neurological function and formation of the cherry-red spot which is the hallmark of TSD. We report the first case of juvenile TSD from Pakistan in a child with death of an older sibling without the diagnosis.

The brain structure and neurosecretory cells of noctuid moth Anadevidia peponis: Noctuidae

1990 ◽  
Vol 48 (3) ◽  
pp. 436-437
Author(s):  
M. Sato ◽  
Y. Ogawa ◽  
M. Sasaki ◽  
T. Matsuo
Keyword(s):  
Biological Clock ◽  
Virgin Female ◽  
Basic Structure ◽  
Fixed Time ◽  
Neurosecretory Cells ◽  
Nerve Cells ◽  
Noctuid Moth ◽  
The Right ◽  
20 Nm ◽  
The Brain

A virgin female of the noctuid moth, a kind of noctuidae that eats cucumis, etc. performs calling at a fixed time of each day, depending on the length of a day. The photoreceptors that induce this calling are located around the neurosecretory cells (NSC) in the central portion of the protocerebrum. Besides, it is considered that the female’s biological clock is located also in the cerebral lobe. In order to elucidate the calling and the function of the biological clock, it is necessary to clarify the basic structure of the brain. The observation results of 12 or 30 day-old noctuid moths showed that their brains are basically composed of an outer and an inner portion-neural lamella (about 2.5 μm) of collagen fibril and perineurium cells. Furthermore, nerve cells surround the cerebral lobes, in which NSCs, mushroom bodies, and central nerve cells, etc. are observed. The NSCs are large-sized (20 to 30 μm dia.) cells, which are located in the pons intercerebralis of the head section and at the rear of the mushroom body (two each on the right and left). Furthermore, the cells were classified into two types: one having many free ribosoms 15 to 20 nm in dia. and the other having granules 150 to 350 nm in dia. (Fig. 1).

Management of Glioblastoma Multiforme by Phytochemicals: Applications of Nanoparticle Based Targeted Drug Delivery System

2020 ◽  
Vol 21 ◽  
Author(s):  
Sayed Md Mumtaz ◽  
Gautam Bhardwaj ◽  
Shikha Goswami ◽  
Rajiv Kumar Tonk ◽  
Ramesh K. Goyal ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Glioblastoma Multiforme ◽  
Drug Delivery System ◽  
Delivery System ◽  
Genetic Disorder ◽  
Drug Regimen ◽  
Brain Regions ◽  
Radio Therapy ◽  
Novel Drug ◽  
The Brain

: The Glioblastoma Multiforme (GBM; grade IV astrocytoma) exhort tumor of star-shaped glial cell in the brain. It is a fast-growing tumor that spreads to nearby brain regions specifically to cerebral hemispheres in frontal and temporal lobes. The etiology of GBM is unknown, but major risk factors are genetic disorder like neurofibromatosis and schwanomatosis which develop the tumor in the nervous system. The management of GBM with chemo-radio therapy leads to resistance and current drug regimen like Temozolomide (TMZ) is less efficacious. The reasons behind failure of drugs are due to DNA alkylation in cell cycle by enzyme DNA guanidase and mitochondrial dysfunction. Naturally occurring bio-active compounds from plants known as phytochemicals, serve as vital sources for anti-cancer drugs. Some typical examples include taxol analogs, vinca alkaloids such as vincristine, vinblastine, podophyllotoxin analogs, camptothecin, curcumin, aloe emodin, quercetin, berberine e.t.c. These phytochemicals often act via regulating molecular pathways which are implicated in growth and progression of cancers. However the challenges posed by the presence of BBB/BBTB to restrict passage of these phytochemicals, culminates in their low bioavailability and relative toxicity. In this review we integrated nanotech as novel drug delivery system to deliver phytochemicals from traditional medicine to the specific site within the brain for the management of GBM.

Rhinosinusitis in the Pediatric Patient with Cystic Fibrosis

2014 ◽  
Vol 10 (3) ◽  
pp. 198-201 ◽  
Author(s):  
Christopher Fundakowski ◽  
Rosemary Ojo ◽  
Ramzi Younis
Keyword(s):  
Cystic Fibrosis ◽  
Autosomal Recessive ◽  
Pediatric Patients ◽  
Surgical Intervention ◽  
Chronic Sinusitis ◽  
Genetic Disorder ◽  
Symptomatic Relief ◽  
Recurrence Rates ◽  
Polyp Recurrence ◽  
Sinonasal Polyposis

Cystic fibrosis (CF) is a common autosomal recessive genetic disorder where a deletion mutation and subsequent downstream alteration in transmembrane regulator proteins results in increased mucus viscosity. CF manifests clinically with chronic multisystem inflammation and recurrent infections. Nearly all children with CF have chronic sinusitis, and a large majority will have concurrent sinonasal polyposis. Chronic sinusitis and sinonasal polyposis in pediatric patients with CF can be managed conservatively initially, though most will fail medical management and require surgical intervention. Unfortunately, symptom resolution is marginal and polyp recurrence rates are high. Currently, no cure exists for CF and the mainstay of treatment is to provide symptomatic relief, and minimize disease morbidity.

The musculature and nervous system of the plerocercoid larva of Dibothriorhynchus grossum (Rud.)

Parasitology ◽  
1941 ◽  
Vol 33 (4) ◽  
pp. 373-389 ◽  
Author(s):  
Gwendolen Rees
Keyword(s):  
Nervous System ◽  
Muscle Mass ◽  
Nerve Cells ◽  
The Body ◽  
Lateral Nerve ◽  
Posterior Median ◽  
The Brain ◽  
Ventral Muscle ◽  
Nerve Cords ◽  
Extrinsic Muscles

1. The structure of the proboscides of the larva of Dibothriorhynchus grossum (Rud.) is described. Each proboscis is provided with four sets of extrinsic muscles, and there is an anterior dorso-ventral muscle mass connected to all four proboscides.2. The musculature of the body and scolex is described.3. The nervous system consists of a brain, two lateral nerve cords, two outer and inner anterior nerves on each side, twenty-five pairs of bothridial nerves to each bothridium, four longitudinal bothridial nerves connecting these latter before their entry into the bothridia, four proboscis nerves arising from the brain, and a series of lateral nerves supplying the lateral regions of the body.4. The so-called ganglia contain no nerve cells, these are present only in the posterior median commissure which is therefore the nerve centre.

scholarly journals L2HGDH Missense Variant in a Cat with L-2-Hydroxyglutaric Aciduria

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 682
Author(s):  
Matthias Christen ◽  
Nils Janzen ◽  
Anne Fraser ◽  
Adrian C. Sewell ◽  
Vidhya Jagannathan ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Genetic Defect ◽  
Clinical Signs ◽  
Missense Variant ◽  
Microcytic Anemia ◽  
Abnormal Behavior ◽  
Functional Candidate Gene ◽  
History Of ◽  
The Brain ◽  
Hydroxyglutaric Acid

A 7-month-old, spayed female, domestic longhair cat with L-2-hydroxyglutaric aciduria (L-2-HGA) was investigated. The aim of this study was to investigate the clinical signs, metabolic changes and underlying genetic defect. The owner of the cat reported a 4-month history of multiple paroxysmal seizure-like episodes, characterized by running around the house, often in circles, with abnormal behavior, bumping into obstacles, salivating and often urinating. The episodes were followed by a period of disorientation and inappetence. Neurological examination revealed an absent bilateral menace response. Routine blood work revealed mild microcytic anemia but biochemistry, ammonia, lactate and pre- and post-prandial bile acids were unremarkable. MRI of the brain identified multifocal, bilaterally symmetrical and T2-weighted hyperintensities within the prosencephalon, mesencephalon and metencephalon, primarily affecting the grey matter. Urinary organic acids identified highly increased levels of L-2-hydroxyglutaric acid. The cat was treated with the anticonvulsants levetiracetam and phenobarbitone and has been seizure-free for 16 months. We sequenced the genome of the affected cat and compared the data to 48 control genomes. L2HGDH, coding for L-2-hydroxyglutarate dehydrogenase, was investigated as the top functional candidate gene. This search revealed a single private protein-changing variant in the affected cat. The identified homozygous variant, XM_023255678.1:c.1301A>G, is predicted to result in an amino acid change in the L2HGDH protein, XP_023111446.1:p.His434Arg. The available clinical and biochemical data together with current knowledge about L2HGDH variants and their functional impact in humans and dogs allow us to classify the p.His434Arg variant as a causative variant for the observed neurological signs in this cat.

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