Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0013362 (dysarthria)
 3,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 53-year-old male patient developed insidious onset of length-dependent painful neuropathy on a background of encephalopathy during prolonged treatment with metronidazole for a cumulative dose of 146 g in 88 days. The reversible encephalopathy was documented with gradual resolution of hyperintense lesions in bilateral cerebellum and brainstem on brain MRI together with the improvement in symptoms of ataxia and dysarthria. The concomitant impairment of small-diameter sensory nerves posed a diagnostic challenge. The authors took advantage of serial skin biopsies to demonstrate reversible metronidazole-induced small-fibre sensory neuropathy, that is, skin denervation after metronidazole and corresponding skin reinnervation with the disappearance of sensory symptoms.
 ...
PMID:Painful neuropathy due to skin denervation after metronidazole-induced neurotoxicity. 2055 81

The classic phenotype of Friedreich ataxia is characterized by dysarthria, progressive limb and trunk ataxia, loss of reflexes, and gait disturbance with the onset of disease before the second decade. Homozygous trinucleotide repeat expansion of GAA in the FXN gene is found in 98% of patients. Two-5% of all patients have a repeat expansion on one allele and a point mutation on the other allele. Atypical phenotype is found in 25% of patients. A 10-year-old boy presented with congenital biliary atresia and progressive gait abnormality. His examination was significant for spastic gait, hyperreflexia, and sensory neuropathy. Genetic testing revealed a compound heterozygous mutation in the FXN gene. The absence of dysarthria and ataxia, retention of reflexes, absence of diabetes, and variable development of cardiomyopathy support a slow progression of disease with compound heterozygous mutation at G130V. Missense mutations are rare causes of Friedreich ataxia that can only be detected by sequencing of the FXN gene. Sequencing of the FXN gene is essential to make an early diagnosis when there is an atypical phenotype.
...
PMID:Atypical Presentation for Friedreich Ataxia in a Child. 2630 74

Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is a newly described condition with onset in adulthood, characterized by progressive balance impairment and sensory disturbances in the lower limbs, which can severely affect patients' quality of life. Its pathogenesis remains obscure and the diagnosis challenging. We described four patients complaining of slowly progressive gait unbalance and sensory disturbances at the feet followed, after a period ranging 2-6 years, by cerebellar dysfunction. All patients showed gait and limb ataxia, positive Romberg sign, cerebellar dysarthria, gaze-evoked nystagmus, absent deep tendon reflexes, and impaired vibratory sensation. Nerve conduction studies revealed axonal sensory neuropathy, brain magnetic resonance imaging showed cerebellar atrophy, and otoneurological investigation demonstrated bilateral vestibular areflexia with impaired vestibulo-ocular reflexes. The diagnosis of CANVAS should be suspected on clinical ground based on homogeneous course of symptoms and signs, and addressed by video-oculography eye movement recording.
 ...
PMID:Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome: a slowly progressive disorder with stereotypical presentation. 2656 12

Sensory ataxic neuropathy with dysarthria and ophthalmoparesis (SANDO) is a rare phenotype resulting from pathogenic variants of mitochondrial DNA polymerase gamma (POLG). We modeled a novel POLG variant, T599P, that causes the SANDO phenotype and another variant at the same residue, p.T599E, to observe their effect on protein function and confirm the pathogenicity of T599P. Through neoteric molecular modeling techniques, we show that changes at the T599 residue position introduce extra rigidity into the surrounding helix-loop-helix, which places steric pressure on nearby nucleotides. We also provide a clinical description of the T599P variant, which was found in a 42-year-old female proband. The proband presented a 1-year history of progressive gait instability, dysarthria and foot numbness. Her neurologic examination revealed ataxic dysarthria, restricted eye movements, head and palatal tremors, reduced lower limb reflexes, distal multimodal sensory loss and a wide, unsteady ataxic gait. Electromyography studies indicated a sensory neuropathy. Whole-exome sequencing was pursued after tests for infectious, inflammatory and paraneoplastic causes were negative.
 ...
PMID:Protein molecular modeling shows residue T599 is critical to wild-type function of POLG and description of a novel variant associated with the SANDO phenotype. 2964 85

COX20/FAM36A encodes a mitochondrial complex IV assembly factor important for COX2 activation. Only one homozygous COX20 missense mutation has been previously described in two separate consanguineous families. We report four subjects with features that include childhood hypotonia, areflexia, ataxia, dysarthria, dystonia, and sensory neuropathy. Exome sequencing in all four subjects identified the same novel COX20 variants. One variant affected the splice donor site of intron-one (c.41A>G), while the other variant (c.157+3G>C) affected the splice donor site of intron-two. cDNA and protein analysis indicated that no full-length cDNA or protein was generated. These subjects expand the phenotype associated with COX20 deficiency.
 ...
PMID:Novel pathogenic COX20 variants causing dysarthria, ataxia, and sensory neuropathy. 3065 93

Friedreich's ataxia is classically considered a disease with onset in the first or second decade. However, late-onset (age of onset 25-39 years) and very-late-onset (age of onset >40 years) forms do occur rarely. Misdiagnosis is common, particularly because the later onset forms of Friedreich's ataxia commonly do not show characteristic features of the disorder (areflexia, dysarthria, sensory neuropathy, extensor plantars, amyotrophy, cardiac involvement, diabetes mellitus, scoliosis). Also, there may be atypical features such as spasticity, brisk reflexes and laryngeal dystonia. We present the clinical, imaging and genetic findings of a kindred with very-late-onset Friedreich's ataxia and discuss the pitfalls and risk of misdiagnosis.
 ...
PMID:Very-late-onset Friedreich's ataxia: diagnosis in a kindred with late-onset cerebellar ataxia. 3146 49

Ataxia, causing imbalance, dizziness and falls, is a leading cause of neurological disability. We have recently identified a biallelic intronic AAGGG repeat expansion in replication factor complex subunit 1 (RFC1) as the cause of cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) and a major cause of late onset ataxia. Here we describe the full spectrum of the disease phenotype in our first 100 genetically confirmed carriers of biallelic repeat expansions in RFC1 and identify the sensory neuropathy as a common feature in all cases to date. All patients were Caucasian and half were sporadic. Patients typically reported progressive unsteadiness starting in the sixth decade. A dry spasmodic cough was also frequently associated and often preceded by decades the onset of walking difficulty. Sensory symptoms, oscillopsia, dysautonomia and dysarthria were also variably associated. The disease seems to follow a pattern of spatial progression from the early involvement of sensory neurons, to the later appearance of vestibular and cerebellar dysfunction. Half of the patients needed walking aids after 10 years of disease duration and a quarter were wheelchair dependent after 15 years. Overall, two-thirds of cases had full CANVAS. Sensory neuropathy was the only manifestation in 15 patients. Sixteen patients additionally showed cerebellar involvement, and six showed vestibular involvement. The disease is very likely to be underdiagnosed. Repeat expansion in RFC1 should be considered in all cases of sensory ataxic neuropathy, particularly, but not only, if cerebellar dysfunction, vestibular involvement and cough coexist.
 ...
PMID:Cerebellar ataxia, neuropathy, vestibular areflexia syndrome due to RFC1 repeat expansion. 3204 May 56


<< Previous 1 2