Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0314719 (dry eye)
 2,625 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antibodies specific for the neuronal ganglionic nicotinic acetylcholine receptor (nAChR) are found in high titer in serum of patients with subacute autonomic failure. This clinical disorder is known as autoimmune autonomic neuropathy (AAN). Rabbits immunized with a neuronal nAChR alpha3 subunit fusion protein produce ganglionic nAChR antibodies and develop autonomic failure (experimental AAN, or EAAN). We used quantitative measures of autonomic function to demonstrate that this animal model of neuronal nAChR autoimmunity recapitulates the cardinal autonomic features of AAN in humans. The severity of dysautonomia in the rabbit ranges from isolated cardiovagal impairment to severe panautonomic failure with fixed mydriasis, gastroparesis, dry eyes, impaired heart rate variability, hypotension, and low plasma catecholamines. The severity of autonomic failure correlates with serum antibody levels. Immunohistochemical staining of superior cervical ganglia and myenteric plexus neurons demonstrates intact presynaptic nerve terminals and intact postsynaptic neurons containing cytoplasmic nAChR, but lacking surface nAChR. These findings define the autonomic physiology and histopathology of this novel animal model and support the concept that AAN in humans is a disorder of ganglionic cholinergic synaptic transmission caused by ganglionic nAChR antibodies.
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PMID:Experimental autoimmune autonomic neuropathy. 1296 72

Autoimmune autonomic ganglionopathy is a disorder of isolated autonomic failure associated with antibodies to the nicotinic acetylcholine receptor of the autonomic ganglia resulting in severe orthostatic intolerance, syncope, constipation, gastroparesis, urinary retention, dry mouth, dry eyes, blurred vision and anhidrosis. We report the autonomic test results, antibody titers and clinical findings in 8 patients with antibodies to the nicotinic acetylcholine receptor of the autonomic ganglia. There was a sigmoidal relation between the antibody titers and the fall in systolic blood pressure (r(2)=0.84). The threshold occurred with antibody titers of approximately 1 nmol/l. Over the linear portion of the sigmoid curve, with antibody titers in the 1-3 nmol/l range, increasing antibody titers resulted in more severe orthostatic hypotension (r=0.94, P<0.001). The saturation point of the sigmoidal relation occurred at approximately 3 nmol/l with drops in systolic blood pressure of approximately 100 mmHg during upright tilt. The antibody titers correlated inversely with the Valsalva ratio (r=-0.87, P<0.001), the 30:15 ratio (r=-0.84, P<0.001) and the expiratory to inspiratory ratio (r=-0.67, P<0.01). Patients with orthostatic intolerance, anhidrosis, constipation, urinary dysfunction, sicca syndrome and pupillary dysfunction had higher antibody titers than subjects that did not (P<0.01 in all cases). Autoimmune autonomic ganglionopathy is a clinically heterogeneous disease with variable presentation, particularly in subjects with lower antibody titers. Our data suggest that patients with higher antibody titers have wide spread dysautonomia while those with lower antibody levels may present with, or evolve into, more focal or restricted presentations.
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PMID:Antibody titers predict clinical features of autoimmune autonomic ganglionopathy. 1914 72

Gain-of-function mutations in the SCN10A gene (encoding the Nav1.8 voltage gated sodium channel) have been reported in a small number of patients. All presented with predominantly painful sensory neuropathy, congruent with the expression of Nav1.8 in nociceptive sensory neurons of the dorsal root ganglion. Only a few had mild autonomic symptoms, including dry eyes and mouth, orthostatic dizziness, palpitations, diarrhea and constipation. The underlying mechanism of the autonomic symptoms in these patients is unclear. We describe a 37-year-old woman with severe progressive gastroparesis and diffuse painful small fiber sensory neuropathy that started at age 32. Due to the severe dysphagia she could not ingest solid food, and lost eight kilograms. The gastroparesis was documented by esophageal manometry and gastric scintigraphy. The neuropathic pain started distally and then intensified and spread to most body areas. The patient harbored a novel heterozygous mutation: c.G4915A:p.D1639N in the SCN10A gene. To the best of our knowledge, this is the first description of such a phenotype due to a Nav1.8 mutation. Thus, our study expands the clinical spectrum of Nav1.8 associated disorders, and suggests that mutations in this sodium channel should be considered in patients with gastrointestinal motility dysfunction and painful neuropathy.
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PMID:Painful small fiber neuropathy with gastroparesis: A new phenotype with a novel mutation in the SCN10A gene. 2671 56