scholarly journals Positioning Head Tilt in Canine Lysosomal Storage Disease: A Retrospective Observational Descriptive Study

2021 ◽  
Vol 8 ◽  
Author(s):  
Shinji Tamura ◽  
Yumiko Tamura ◽  
Yuya Nakamoto ◽  
Daisuke Hasegawa ◽  
Masaya Tsuboi ◽  
...  
Keyword(s):  
Lysosomal Storage Disease ◽  
Storage Disease ◽  
Neuronal Degeneration ◽  
Neuronal Ceroid Lipofuscinosis ◽  
Clinical Signs ◽  
Head Tilt ◽  
Vestibular Nuclei ◽  
Lysosomal Storage ◽  
Gm2 Gangliosidosis ◽  
Gm1 Gangliosidosis

Positioning head tilt is a neurological sign that has recently been described in dogs with congenital cerebellar malformations. This head tilt is triggered in response to head movement and is believed to be caused by a lack of inhibition of the vestibular nuclei by the cerebellar nodulus and ventral uvula (NU), as originally reported cases were dogs with NU hypoplasia. We hypothesized that other diseases, such as lysosomal storage diseases that cause degeneration in the whole brain, including NU, may cause NU dysfunction and positioning head tilt. Videos of the clinical signs of canine lysosomal storage disease were retrospectively evaluated. In addition, post-mortem NU specimens from each dog were histopathologically evaluated. Nine dogs were included, five with lysosomal storage disease, two Chihuahuas with neuronal ceroid lipofuscinosis (NCL), two Border Collies with NCL, one Shikoku Inu with NCL, two Toy Poodles with GM2 gangliosidosis, and two Shiba Inus with GM1 gangliosidosis. Twenty-eight videos recorded the clinical signs of the dogs. In these videos, positioning head tilt was observed in seven of nine dogs, two Chihuahuas with NCL, one Border Collie with NCL, one Shikoku Inu with NCL, one Toy Poodle with GM2 gangliosidosis, and two Shiba Inus with GM1 gangliosidosis. Neuronal degeneration and loss of NU were histopathologically confirmed in all diseases. As positioning head tilt had not been described until 2016, it may have been overlooked and may be a common clinical sign and pathophysiology in dogs with NU dysfunction.

scholarly journals Surf4 Promotes Endoplasmic Reticulum Exit of the Lysosomal Prosaposin-Progranulin Complex

2021 ◽  
Author(s):  
S. Devireddy ◽  
S.M. Ferguson
Keyword(s):  
Endoplasmic Reticulum ◽  
Frontotemporal Dementia ◽  
Lysosomal Storage Disease ◽  
Intracellular Trafficking ◽  
Secretory Pathway ◽  
Storage Disease ◽  
Neuronal Ceroid Lipofuscinosis ◽  
Lysosomal Storage ◽  
Efficient Delivery ◽  
Lysosomal Protein

AbstractProgranulin is a lysosomal protein whose haploinsufficiency causes frontotemporal dementia while homozygous loss of progranulin causes neuronal ceroid lipofuscinosis, a lysosomal storage disease. The sensitivity of cells to progranulin deficiency raises important questions about how cells coordinate intracellular trafficking of progranulin to ensure its efficient delivery to lysosomes. In this study, we discover that progranulin interacts with prosaposin, another lysosomal protein, within the lumen of the endoplasmic reticulum (ER) and that prosaposin is required for the efficient ER exit of progranulin. Mechanistically, we identify an interaction between prosaposin and Surf4, a receptor that promotes loading of lumenal cargos into COPII coated vesicles, and establish that Surf4 is critical for the efficient export of progranulin and prosaposin from the ER. Collectively, this work demonstrates a network of interactions occurring early in the secretory pathway that promote the ER exit and subsequent lysosomal delivery of newly translated progranulin and prosaposin.

Efficient progranulin exit from the ER requires its interaction with prosaposin, a Surf4 cargo

2021 ◽  
Vol 221 (2) ◽  
Author(s):  
Swathi Devireddy ◽  
Shawn M. Ferguson
Keyword(s):  
Endoplasmic Reticulum ◽  
Frontotemporal Dementia ◽  
Lysosomal Storage Disease ◽  
Intracellular Trafficking ◽  
Secretory Pathway ◽  
Storage Disease ◽  
Neuronal Ceroid Lipofuscinosis ◽  
Lysosomal Storage ◽  
Efficient Delivery ◽  
Lysosomal Protein

Progranulin is a lysosomal protein whose haploinsufficiency causes frontotemporal dementia, while homozygous loss of progranulin causes neuronal ceroid lipofuscinosis, a lysosomal storage disease. The sensitivity of cells to progranulin deficiency raises important questions about how cells coordinate intracellular trafficking of progranulin to ensure its efficient delivery to lysosomes. In this study, we discover that progranulin interactions with prosaposin, another lysosomal protein, first occur within the lumen of the endoplasmic reticulum (ER) and are required for the efficient ER exit of progranulin. Mechanistically, we identify an interaction between prosaposin and Surf4, a receptor that promotes loading of lumenal cargos into COPII-coated vesicles, and establish that Surf4 is critical for the efficient export of progranulin and prosaposin from the ER. Collectively, this work demonstrates that a network of interactions occurring early in the secretory pathway promote the ER exit and subsequent lysosomal delivery of newly translated progranulin and prosaposin.

scholarly journals Lysosomal Storage Disease

2009 ◽  
Vol 48 (175) ◽  
Author(s):  
Binod Khatiwada ◽  
A Pokharel
Keyword(s):  
Lysosomal Storage Disease ◽  
Lysosomal Enzyme ◽  
Enzyme Assay ◽  
Storage Disease ◽  
Lysosomal Storage ◽  
Gm1 Gangliosidosis ◽  
Poor Vision ◽  
Gradual Onset ◽  
History Of ◽  
Beta Galactosidase

We report a case of lysosomal storage disease diagnosed by lysosomal enzyme assay in a two year oldboy with a history of gradual onset of weakness of body, poor vision, fl accid neck and spasticity in allfour limbs with hyper-refl exia. On fundus examination cherry red spots were noted at macula. Onperforming lysosomal enzyme assay, beta-galactosidase level was considerably low. This indicatesthat the child is affected by lysosomal storage disease most likely GM1 gangliosidosis. The diagnosisis important because the disease is rare and it may be missed as the symptoms are similar to otherneurological conditions and the diagnosis can help with future conception.Key Words: beta-galactosidase, GM1 gangliosidosis, lysosomal storage disease

Diagnostic challenge for the rare lysosomal storage disease: Late infantile GM1 gangliosidosis

2018 ◽  
Vol 40 (5) ◽  
pp. 383-390 ◽  
Author(s):  
Jin Sook Lee ◽  
Jong-Moon Choi ◽  
Moses Lee ◽  
Soo Yeon Kim ◽  
Sangmoon Lee ◽  
...  
Keyword(s):  
Lysosomal Storage Disease ◽  
Storage Disease ◽  
Lysosomal Storage ◽  
Diagnostic Challenge ◽  
Gm1 Gangliosidosis

GM2 Gangliosidosis Variant 0 (Sandhoff Disease) in a Mixed-Breed Dog

2015 ◽  
Vol 51 (6) ◽  
pp. 396-400 ◽  
Author(s):  
Moeko Kohyama ◽  
Akira Yabuki ◽  
Yasuaki Kawasaki ◽  
Hiroaki Kawaguchi ◽  
Naoki Miura ◽  
...  
Keyword(s):  
Lysosomal Storage Disease ◽  
Storage Disease ◽  
Sandhoff Disease ◽  
Lysosomal Storage ◽  
Gm2 Gangliosidosis ◽  
Visual Deficits ◽  
Neurological Signs ◽  
The Third ◽  
Mixed Breed ◽  
First Time

GM2 gangliosidosis variant 0 (Sandhoff disease, SD) is a fatal, progressive, neurodegenerative lysosomal storage disease caused by simultaneous deficiencies of acid β-hexosaminidases A and B. Canine SD has so far been identified only in two purebreeds. In this article, we present the case of a 10 mo old, male dog of mixed breed that developed progressive neurological signs including ataxia, postural deficit, and visual deficits and finally died at the age of 21 mo. The dog was diagnosed with SD on the basis of the results of biochemical and histopathological analyses. This is the third report of canine SD and the first time it has been identified in a mixed breed.

scholarly journals Tremorgenic syndrome caused by Ipomoea pes caprae in cattle

2020 ◽  
Vol 40 (6) ◽  
pp. 443-450
Author(s):  
Flávio A.S. Graça ◽  
Mariana S. d’Avila ◽  
Ticiana N. França ◽  
Aníbal G. Armién ◽  
Marcia F. Rolim ◽  
...  
Keyword(s):  
Purkinje Cells ◽  
Lysosomal Storage Disease ◽  
Storage Disease ◽  
Histopathological Examination ◽  
Clinical Signs ◽  
Lysosomal Storage ◽  
Adult Cattle ◽  
Histological Lesion ◽  
Cerebellar Purkinje Cells ◽  
Clinical Changes

ABSTRACT: Poisonous plants are a significant cause of death among adult cattle in Brazil. Plants that affect the central nervous system are widely spread throughout the Brazilian territory and comprise over 30 toxic species, including the genus Ipomoea, commonly associated with a lysosomal storage disease and a tremorgenic syndrome in livestock. We describe natural and experimental Ipomoea pes caprae poisoning in cattle from a herd in the Northside of Rio de Janeiro, Brazil. Affected cattle presented episodes of severe ataxia, abnormal posture followed by falling, muscular tremor, contraction, and spasticity, more prominent in the limbs, intensified by movement and forthcoming, and recumbence. Grossly, a substantial amount of leaves and petioles were found in the rumen. Histopathological examination showed degenerative neuronal changes, mostly in cerebellar Purkinje cells, which were confirmed with Bielschowsky silver. The characteristic clinical changes and mild histological lesion strongly suggested a tremorgenic syndrome. Lectin- immunohistochemistry evaluation reinforced this hypothesis; all lectins tested failed to react with affect neurons and Purkinje cells, which ruled out an underlying lysosomal storage disease. One calf given I. pes caprae leaves experimentally developed clinical signs similar to natural cases. On the 28th day of the experiment, the plant administration was suspended, and the calf recovered within four days. I. pes caprae’s spontaneous tremorgenic syndrome in cattle is conditioned to exclusive feeding for several months. We were able to experimentally reproduce toxic clinical signs 12 days following the ingestion.

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