Beyond neuropathy in hereditary sensory and autonomic neuropathy type V: cognitive evaluation

Andrade, Daniel Ciampi de; Baudic, Sophie; Attal, Nadine; Rodrigues, Cleonísio Leite; Caramelli, Paulo; Lino, Angelina Maria Martins; Marchiori, P E; Okada, Massako; Scaff, Milberto; Bouhassira, Didier; Teixeira, Manoel Jacobsen

doi:10.1111/j.1468-1331.2008.02172.x

Cited by 23 publications

(16 citation statements)

References 40 publications

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“…HSAN IV patients show a severe pain insensitivity, anhydrosis and mental retardation, which have been interpreted as due to the developmental consequences of lack of trophic support by the NGF/TrkA system to target neurons, including sensory neurons [26]. Importantly, HSAN V patients, differently from HSAN IV patients, while displaying a similar congenital insensitivity to pain, show no mental retardation nor other neurological and cognitive deficits [29], suggesting that neurodevelopmental effects on NGF target neurons, including sensory neurons, are probably minor in HSAN V patients. The single nucleotide missense mutation in the NGFB gene, found in a family of HSAN V patients, who show impaired temperature sensation and an almost complete loss of deep pain perception [27], but normal sweating [30], results in the aminoacid R to W substitution at position 100 of mature NGF protein [27].…”

Section: Introductionmentioning

confidence: 99%

Taking Pain Out of NGF: A “Painless” NGF Mutant, Linked to Hereditary Sensory Autonomic Neuropathy Type V, with Full Neurotrophic Activity

Covaceuszach²,

et al. 2011

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During adulthood, the neurotrophin Nerve Growth Factor (NGF) sensitizes nociceptors, thereby increasing the response to noxious stimuli. The relationship between NGF and pain is supported by genetic evidence: mutations in the NGF TrkA receptor in patients affected by an hereditary rare disease (Hereditary Sensory and Autonomic Neuropathy type IV, HSAN IV) determine a congenital form of severe pain insensitivity, with mental retardation, while a mutation in NGFB gene, leading to the aminoacid substitution R100W in mature NGF, determines a similar loss of pain perception, without overt cognitive neurological defects (HSAN V). The R100W mutation provokes a reduced processing of proNGF to mature NGF in cultured cells and a higher percentage of neurotrophin secreted is in the proNGF form. Moreover, using Surface Plasmon Resonance we showed that the R100W mutation does not affect NGF binding to TrkA, while it abolishes NGF binding to p75NTR receptors. However, it remains to be clarified whether the major impact of the mutation is on the biological function of proNGF or of mature NGF and to what extent the effects of the R100W mutation on the HSAN V clinical phenotype are developmental, or whether they reflect an impaired effectiveness of NGF to regulate and mediate nociceptive transmission in adult sensory neurons. Here we show that the R100 mutation selectively alters some of the signaling pathways activated downstream of TrkA NGF receptors. NGFR100 mutants maintain identical neurotrophic and neuroprotective properties in a variety of cell assays, while displaying a significantly reduced pain-inducing activity in vivo (n = 8–10 mice/group). We also show that proNGF has a significantly reduced nociceptive activity, with respect to NGF. Both sets of results jointly contribute to elucidating the mechanisms underlying the clinical HSAN V manifestations, and to clarifying which receptors and intracellular signaling cascades participate in the pain sensitizing action of NGF.

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Section: Introductionmentioning

confidence: 99%

Taking Pain Out of NGF: A “Painless” NGF Mutant, Linked to Hereditary Sensory Autonomic Neuropathy Type V, with Full Neurotrophic Activity

Covaceuszach²,

et al. 2011

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“…[6][7][8] In HSAN type V, there is severe reduction of unmyelinated nerve fibres and a moderate loss of thin myelinated nerve fibres whereas HSAN type IV show reduced small myelinated nerve fibres and normal large myelinated nerve fibres. 9,10 Self-mutilation and impairment of pain sensation is also seen in conditions such as Lesch-Nyhan syndrome and de Lange syndrome. 11 However HSAN type V can be differentiated from these syndromes by the presence of partial anhydrosis, absence of peripheral nerve thickening and dysmorphic features, a normal serum uric acid level and electrophysiological studies and histopathological findings of nerve fiber loss.…”

Section: Discussionmentioning

confidence: 99%

Hereditary sensory autonomic neuropathy type V: a rare case report

Madhura

Sowrabha

Manjunath

et al. 2018

Int J Contemp Pediatr

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Hereditary sensory autonomic neuropathy (HSAN) type V is a rare autosomal recessive condition caused by mutation in neurotrophic tyrosine kinase receptor type 1 gene located on chromosome 1 (1q21-1q22). It is characterized by pain insensitivity, partial anhydrosis without mental retardation and unimpaired touch and pressure sensitivity. Self-mutilation injury involving teeth, lips, tongue, ears, eyes, nose and fingers are invariable feature of this disorder. This rare disorder can be extremely challenging for the physicians as the symptoms like pain, tenderness is absent and hence most of the symptoms and injuries are frequently missed. Here we report a case of 1-year old female child with HSAN type V, having the typical clinical manifestations of pain insensitivity causing self-mutilation. Apart from the classical manifestations of HSAN type V, our case also had bilateral corneal opacity.

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“…Our patient presents insensitivity to pain, absence of mental retardation and notably self-mutilation of her fingers, lips and tongue. All this clinical manifestations are reported in the literature and found in the rare published cases [1,[4][5][6][7][8]. EMG exploration was in favor of sensitive neuropathy.…”

Section: Discussionmentioning

confidence: 99%

“…Hereditary sensory and autonomic neuropathies (HSAN) are autosomal recessive disorders characterized by the loss of deep pain perception [1]. Six types of sensory neuropathies are reported in the literature [2], with different prevalence and clinical features.…”

Section: Introductionmentioning

confidence: 99%