Fabry′s disease: An ultrastructural study of nerve biopsy

Gayathri, Narayanappa; Yasha, T C; Kanjalkar, Makarand; Agarwal, S. K.; Sagar, B. K. Chandrashekar; Santosh, Vani; Shankar, S K

doi:10.4103/0972-2327.42939

Cited by 6 publications

(7 citation statements)

References 6 publications

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“…31,32 A second hypothesis concerns chronic nerve ischemia secondary to Gl 3 deposition within the endothelial cells of the blood vessels supplying nerve fibers. 28 Lyso-Gl 3 has been shown to promote SMC proliferation in vitro and has been proposed to play a role in the development of vascular pathology in FD. 33 Another possible hypothesis is that the increase in the number of small regenerating unmyelinated fibers as seen in some cases 34 in spite of the pattern of nerve fiber depletion generates hyperexcitability and spontaneous firing of sprouting unmyelinated neurites arising from nociceptive axons.…”

Section: Introductionmentioning

confidence: 99%

Small Fiber Neuropathy in Fabry Disease: a Review of Pathophysiology and Treatment

Politei

Durand

Schenone

2016

Journal of Inborn Errors of Metabolism and Screening

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Fabry disease is an inherited metabolic disorder characterized by progressive lysosomal accumulation of glycolipids in a variety of cell types, including neural cells. Small, unmyelinated nerve fibers are particularly affected and small fiber peripheral neuropathy often clinically manifests at a young age. Neuropathic pain and pain attacks are often the presenting symptoms of the disease and start at an average age of 9 years in male patients and 16 years in female patients, but currently a systematic literature review in early childhood showed the presence of these symptoms before the age of 5 years. Clinical studies have shown that enzyme replacement therapy may improve the overall pain scores and pain intensity in patients; improvements in pain outcomes have been sustained during the long-term follow-up, allowing many patients to reduce their use of pain medication. Some indirect evidence from dose-switching studies suggests that enzyme replacement therapy dose may be of relevance to pain outcomes. Considering that damage to small nerve fibers occurs early, prompt treatment is important in order to limit damage to the peripheral nervous system. In this article a comprehensive overview of the existing literature on small nerve fiber pathophysiology and the relationship with neuropathic pain and treatment response in children and adults with Fabry disease is presented.

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Section: Introductionmentioning

confidence: 99%

Small Fiber Neuropathy in Fabry Disease: a Review of Pathophysiology and Treatment

Politei

Durand

Schenone

2016

Journal of Inborn Errors of Metabolism and Screening

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“…reported a 19 yr old boy who presented with acroparasthesias, angiokeratomas and corneal opacities and nerve biopsy by electron microscopy revealed lamellated inclusions in the smooth muscles, perineurial and endothelial cells characteristic of Fabrys disease. [6] This child however did not have cardiac and renal involvement as our child.…”

Section: Discussionmentioning

confidence: 65%

Burning feet, dilated heart and failed kidneys

Abraham²,

Nadig

et al. 2019

Indian J Nephrol

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“…Swelling of the dorsal root ganglion neurons and accumulation of Gb3 in the cytoplasm of these cells were also reported in human autopsy samples [35,36] and in α-galactosidase knock out animals [28,29]. In human sural nerve biopsy material ultrastructural morphometric analysis showed a reduction of the number of both small diameter myelinated axons and unmyelinated axons [36] and appearance of regenerating clusters was also reported [36,37]. Although numerous studies described alterations in the heat or cold thresholds of cutaneous sensory nerves [38,39] and the reduced mechanical sensitivity of the cornea [32,34], observations reporting the specific impairment of chemosensitive C-fiber neurons is sparse.…”

Section: Human Diseases Affecting Glycosphingolipid Metabolism and Painmentioning

confidence: 73%

“…Although it is plausible to assume that accumulation of the breakdown products of the glycosphingolipid catabolism may be an important causative factor, significant accumulation of lipids in the axons of peripheral nerves (especially in unmyelinated fibers) has been rarely observed. In biopsy specimens obtained from affected patients, accumulation of lipids in form of storage vesicles and lamellated bodies is prevalent in vascular endothelial cells and fibroblasts (perineural and endoneurial) [36,37]. Despite the less conspicuous accumulation of glycosphingolipids in the peripheral nociceptive axons the significance of the disturbed glycosphingolipid metabolism in nociceptive processing has been supported by some recent findings.…”

Section: Human Diseases Affecting Glycosphingolipid Metabolism and Painmentioning

confidence: 95%

Role of Gangliosides in Peripheral Pain Mechanisms

Stella

Dobos

Kis

et al. 2020

IJMS

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Gangliosides are abundantly occurring sialylated glycosphingolipids serving diverse functions in the nervous system. Membrane-localized gangliosides are important components of lipid microdomains (rafts) which determine the distribution of and the interaction among specific membrane proteins. Different classes of gangliosides are expressed in nociceptive primary sensory neurons involved in the transmission of nerve impulses evoked by noxious mechanical, thermal, and chemical stimuli. Gangliosides, in particular GM1, have been shown to participate in the regulation of the function of ion channels, such as transient receptor potential vanilloid type 1 (TRPV1), a molecular integrator of noxious stimuli of distinct nature. Gangliosides may influence nociceptive functions through their association with lipid rafts participating in the organization of functional assemblies of specific nociceptive ion channels with neurotrophins, membrane receptors, and intracellular signaling pathways. Genetic and experimentally induced alterations in the expression and/or metabolism of distinct ganglioside species are involved in pathologies associated with nerve injuries, neuropathic, and inflammatory pain in both men and animals. Genetic and/or pharmacological manipulation of neuronal ganglioside expression, metabolism, and action may offer a novel approach to understanding and management of pain.

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Fabry′s disease: An ultrastructural study of nerve biopsy

Cited by 6 publications

References 6 publications

Small Fiber Neuropathy in Fabry Disease: a Review of Pathophysiology and Treatment

Small Fiber Neuropathy in Fabry Disease: a Review of Pathophysiology and Treatment

Burning feet, dilated heart and failed kidneys

Role of Gangliosides in Peripheral Pain Mechanisms

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