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Results for “axonal sensorimotor neuropathy”

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7 recordsLinked to original sources

PubMed2024

Dominant NARS1 mutations causing axonal Charcot-Marie-Tooth disease expand NARS1-associated diseases.

Pathogenic variants in six aminoacyl-tRNA synthetase (ARS) genes are implicated in neurological disorders, most notably inherited peripheral neuropathies. ARSs are enzymes that charge tRNA molecules with cognate amino acids. Pathogenic variants in asparaginyl-tRNA synthetase (NARS1) cause a neurological phenotype combining developmental delay, ataxia and demyelinating peripheral neuropathy. NARS1 has not yet been linked to axonal Charcot-Marie-Tooth disease. Exome sequencing of patients with inherited peripheral neuropathies revealed three previously unreported heterozygous NARS1 variants in three families. Clinical and electrophysiological details were assessed. We further characterized all three variants in a yeast complementation model and used a knock-in mouse model to study variant p.Ser461Phe. All three variants (p.Met236del, p.Cys342Tyr and p.Ser461Phe) co-segregate with the sensorimotor axonal neuropathy phenotype. Yeast complementation assays show that none of the three NARS1 variants support wild-type yeast growth when tested in isolation (i.e. in the absence of a wild-type copy of NARS1), consistent with a loss-of-function effect. Similarly, the homozygous knock-in mouse model (p.Ser461Phe/Ser472Phe in mouse) also demonstrated loss-of-function characteristics. We present three previously unreported NARS1 variants segregating with a sensorimotor neuropathy phenotype in three families. Functional studies in yeast and mouse support variant pathogenicity. Thus, NARS1 is the seventh ARS implicated in dominant axonal Charcot-Marie-Tooth disease, further stressing that all dimeric ARSs should be evaluated for Charcot-Marie-Tooth disease.

Charcot–Marie–Tooth disease↗

PubMed2025

Ataxia and oculomotor apraxia caused by a large-scale deletion in the senataxin gene.

Senataxin, an RNA/DNA helicase, is a key protein providing genome stability and one of the best characterized R-loop-binding factors playing an important role in transcription and DNA repair processes. Pathogenic SETX gene variants cause autosomal recessive spinocerebellar ataxia with axonal neuropathy (AOA2, MIM #606002) and autosomal dominant juvenile amyotrophic lateral sclerosis (ALS4, MIM #602433), rare neurodegenerative disorders characterized by juvenile onset of progressive cerebellar ataxia, axonal sensorimotor peripheral neuropathy, combined upper and lower motor neuron symptoms, and increased serum alpha-fetoprotein (AFP; specific for AOA2). We report two cases of adult patients presenting with cerebellar syndrome, scanned speech, and exercise intolerance which started in the second/third decade of life and were followed by muscle weakness and impaired gait coordination. Whole exome sequencing (WES) was performed to analyze single nucleotide and copy number variants. A decreased coverage of a genomic region of around 16 kb on chromosome 9 (chr9:132,295,852-132,311,876), suggesting a deletion encompassing 5 exons of the SETX gene (exons 11-15, NM_015046.7) was observed. This homozygous SETX (9q34.13) deletion leads to a frame shift and consequently truncation of the helicase domain in the protein. Loss-of-function variants in the SETX gene are known to be pathogenic. Statistical analysis of NGS data from the Polish population identified a few heterozygous carriers, suggesting its region-specific origin.

Humans↗

PubMed1979

Acute generalized polyneuropathy accompanying lithium poisoning.

A woman with typical symptoms of lithium toxicity had, in addition, severe generalized sensorimotor peripheral neuropathy, which cleared completely as the recovered. Electrodiagnostic studies suggested axonal lesions; autopsy ten months later revealed no residual abnormalities. Previous studies have shown that lithium can affect peripheral nerve function, but this is the first reported case of peripheral neuropathy in association with lithium toxicity.

Adolescent↗

PubMed1977

The peroneal muscular atrophy syndrome. Clinical, genetic, electrophysiological and nerve biopsy studies. Part 2. Observations on pathological changes in sural nerve biopsies.

The light-and electron-microscopic, single teased nerve and morphometric studies of a series of 17 sural nerve biopsies from patients with personeal muscular atrophy are presented. The cases are divided into the following groups according to the criteria of Davis, Bradley and Madrid (1977): Hypertrophic Neuropathy Group; Intermediate Group; Neuronal Sensorimotor Group; Neuronal Motor Group. The Hypertrophic Neuropathy Group had nerve hypertrophy and marked segmental demyelination and onion bulb formation. The Intermediate Group also had segmental demyelilination and onion bulb formation, but nerve hypertrophy was not seen, and axonal degeneration and regeneration were prominent. The Neuronal Sensorimotor Group cases were all sporadic, and showed some onion bulbs, paranodal demyelination and evidence of axonal degeneration and regeneration. The sensory nerve biopsy in the Neuronal Motor Group showed no major abnormality apart from some cluster formation indicating axonal regeneration. The data tend to support the classification of peroneal muscular atrophy proposed by Davis et al. (1977), though there was overlap between the groups in individual pathological parameters.

Adolescent↗

PubMed1976

Glue sniffer's neuropathy.

Progressive sensorimotor neuropathy developed in two patients exposed to prolonged (chronic) inhalation of n-hexane (glue sniffing). Sural nerve biopsies showed loss of axons; remaining axons were either normal or showed accumulation of filaments of 90 to 100 A thick, widened nodes of Ranvier, and focal enlargements. The muscle biopsy revealed neurogenic atrophy. Intramuscular nerve twigs and end-plates, studied in one patient, showed loss of axons and nerve terminals. Unmyelinated axons also showed accululation of 60 to 100 A thick filaments. The similarities between the pathologic findings in the peripheral nerve of these patients and those with acrylamide neuropathy suggest that the n-hexane inhalation produces a dying back neuropathy.

Adult↗

PubMed1979

The natural history of peripheral neuropathy in primary systemic amyloidosis.

The records of 31 patients with primary systemic amyloidosis and peripheral neuropathy seen during a 17-year period were analyzed to define the natural history of the neuropathy. Patients tended to be older men with a painful, distal, symmetrical sensorimotor neuropathy and prominent autonomic features. Loss of pain and temperature sensation was frequently more striking than loss of mechanoreception. Renal, cardiac, hematological, and gastrointestinal dysfunction often overshadowed the neuropathy. Clinical, neurophysiological, and histopathological studies pointed to axonal degeneration with predominant but not exclusive involvement of small myelinated and unmyelinated fibers. The neuropathy was progressive in all patients with or without treatment, but death was typically due to supervening medical complications.

Aged↗

PubMed1976

Non-hypertrophic familial neuropathy associated with intention tremor. A variety of Charcot-Marie-Tooth disease?

A family with an association of sensorimotor neuropathy and intention tremor is reported. Clinical examination of 3 affected family members showed in varying degrees areflexia, muscle wasting, impairment of deep sensation with an ataxic gait, pes cavus and disabling intention tremor. Motor nerve conduction velocities were moderately slowed. A superficial peroneal nerve biopsy showed axonal degeneration without segmental demyelination or onion bulb formation. Our observation seems to indicate an association of intention tremor with the non-hypertrophic variety of Charcot-Marie-Tooth disease. It can therefore be suggested that the two classical types of Charcot-Marie-Tooth syndrome possess variants which are associated with intention tremor. This association is well-known for the hypertrophic type; our report gives an example of the non-hypertrophic type.

Adult↗