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Medicina (Kaunas, Lithuania) Jul 2022Harlequin syndrome (HS) is a rare autonomic disorder. The causes and risk factors of the disease are not fully understood. Some cases of HS are associated with traumatic... (Review)
Review
Harlequin syndrome (HS) is a rare autonomic disorder. The causes and risk factors of the disease are not fully understood. Some cases of HS are associated with traumatic injuries, tumors, or vascular impairments of the head. Symptoms of HS can also occur in some autoimmune disorders, ophthalmic disorders, sleep disorders, and with certain organic lesions. In this context, a thorough review of the pathophysiology of HS in relation to neurological, ophthalmological, and dermatological conditions is necessary. In this mini-review, we aim to review the pathophysiological changes and underlying mechanisms in primary and secondary HS. Additionally, we discuss possible management approaches for patients with HS in light of the discussed pathological mechanisms. The main symptoms of HS that are correlated with autonomic nervous system impairments include sudden unilateral flushing of the face, neck, chest, and rarely arm, with concurrent contralateral anhidrosis. Despite reported co-occurring syndromes (such as cluster headaches), several studies have shown that HS could frequently overlap with other syndromes that are disruptive to the idiopathic nerve pathways. HS usually does not require any medical treatment. In some severe cases, symptomatic treatments could be needed. However, total symptomatic relief may not be achieved in many cases of HS. We therefore suggest an approach to comprehensive management of HS, which may lead to better long-term control of HS.
Topics: Autonomic Nervous System Diseases; Face; Flushing; Humans; Hypohidrosis; Primary Dysautonomias; Rare Diseases
PubMed: 35888657
DOI: 10.3390/medicina58070938 -
Neurology Aug 2020To determine predicting factors and frequency of phenoconversion from pure autonomic failure (PAF) into a synucleinopathy with motor or cognitive involvement of multiple...
OBJECTIVE
To determine predicting factors and frequency of phenoconversion from pure autonomic failure (PAF) into a synucleinopathy with motor or cognitive involvement of multiple system atrophy (MSA), Parkinson disease (PD), or dementia with Lewy bodies (DLB).
METHODS
We performed a retrospective review of all patients with PAF from 2001 to 2011 evaluated at Mayo Clinic, Rochester. Clinical follow-up and patient telephone calls were used to assess for development of symptoms and diagnosis of MSA, PD, or DLB. Clinical and laboratory variables were extracted with factors predictive of evolution assessed using group comparison, odds ratio, and logistical regression.
RESULTS
Among 275 patients with PAF at presentation, 67 (24%) phenoconverted to a synucleinopathy with motor or cognitive involvement; 34 met criteria for MSA, while 33 met criteria for PD or DLB. Age at onset was younger in MSA phenoconverters. Clinical features at presentation influenced phenoconversion: severe bladder symptoms were more common in MSA phenoconverters; subtle motor signs were more frequent in MSA and PD/DLB phenoconverters. MSA phenoconverters were more likely to have higher supine norepinephrine levels and preganglionic pattern of anhidrosis. Presentation variables predicting MSA phenoconversion included subtle motor signs, supine norepinephrine levels, severe bladder symptoms, and dream enactment behavior. Presentation variables predictive of PD/DLB phenoconversion included subtle motor signs, dream enactment behavior, and constipation.
CONCLUSIONS
Our findings suggest that at least a quarter of patients with PAF phenoconvert to MSA, PD, or DLB. Presentation features determine patients at risk for evolution with specific patterns indicative of phenoconversion to MSA vs PD/DLB.
CLASSIFICATION OF EVIDENCE
This study provides Class II evidence that several presentation variables including subtle motor signs, severe bladder symptoms, and dream enactment behavior are associated with an increased risk of developing a synucleinopathy with motor or cognitive involvement.
Topics: Age of Onset; Aged; Female; Humans; Lewy Body Disease; Male; Middle Aged; Multiple System Atrophy; Parkinson Disease; Predictive Value of Tests; Pure Autonomic Failure; REM Sleep Behavior Disorder; Retrospective Studies
PubMed: 32546656
DOI: 10.1212/WNL.0000000000010002 -
International Journal of Molecular... Aug 2021Acquired idiopathic generalized anhidrosis (AIGA) is a rare disorder in which systemic anhidrosis/hypohidrosis occurs without causative dermatological, metabolic or... (Review)
Review
Acquired idiopathic generalized anhidrosis (AIGA) is a rare disorder in which systemic anhidrosis/hypohidrosis occurs without causative dermatological, metabolic or neurological disorder. Most cases of AIGA have been reported in Asia, especially in Japan, but there have been only a few reports in Europe and the United States. Severe AIGA may result in heatstroke and can reduce quality of life due to restriction of exercise and outdoor works. AIGA is often accompanied by cholinergic urticaria (CholU), and it is thought that AIGA and CholU with anhidrosis/hypohidrosis belong to the same spectrum of the disease. However, the pathophysiology of AIGA has not yet been clarified. Decreased expression of cholinergic receptor M3 on the epithelial cells of eccrine sweat glands is often accompanied by T cell infiltration around eccrine apparatus, suggesting an immunological mechanism of disordered perspiration. AIGA is occasionally associated with various complications indicative of autoimmune disorders. The association of autoimmune complications further suggests that AIGA is an autoimmune disorder. Studies on complications may lead to a better understanding of the pathophysiology of AIGA.
Topics: Animals; Autoimmune Diseases; Humans; Hypohidrosis; Receptor, Muscarinic M3; Receptors, Cholinergic; Urticaria
PubMed: 34445091
DOI: 10.3390/ijms22168389 -
Proceedings of the National Academy of... Dec 2023The atypical protein kinase ALPK1 is activated by the bacterial nucleotide sugar ADP-heptose and phosphorylates TIFA to switch on a signaling pathway that combats...
The atypical protein kinase ALPK1 is activated by the bacterial nucleotide sugar ADP-heptose and phosphorylates TIFA to switch on a signaling pathway that combats microbial infection. In contrast, ALPK1 mutations cause two human diseases: the ALPK1[T237M] and ALPK1[Y254C] mutations underlie ROSAH syndrome (retinal dystrophy, optic nerve oedema, splenomegaly, anhidrosis, and migraine headache), while the ALPK1[V1092A] mutation accounts for 45% of spiradenoma and 30% of spiradenocarcinoma cases studied. In this study, we demonstrate that unlike wild-type (WT) ALPK1, the disease-causing ALPK1 mutants trigger the TIFA-dependent activation of an NF-κB/activator protein 1 reporter gene in the absence of ADP-heptose, which can be suppressed by either of two additional mutations in the ADP-heptose binding site that prevent the activation of WT ALPK1 by ADP-heptose. These observations are explained by our key finding that although ALPK1[T237M] and ALPK1[V1092A] are activated by bacterial ADP-heptose, they can also be activated by nucleotide sugars present in human cells (UDP-mannose, ADP-ribose, and cyclic ADP-ribose) which can be prevented by disruption of the ADP-heptose binding site. The ALPK1[V1092A] mutant was also activated by GDP-mannose, which did not activate ALPK1[T237M]. These are new examples of disease-causing mutations permitting the allosteric activation of an enzyme by endogenous molecules that the WT enzyme does not respond to. We propose that the loss of the specificity of ALPK1 for bacterial ADP-heptose underlies ROSAH syndrome and spiradenoma/spiradenocarcinoma caused by ALPK1 mutation.
Topics: Humans; Nucleotides; Sugars; Splenomegaly; Acrospiroma; Mannose; Sweat Gland Neoplasms; Heptoses
PubMed: 38060563
DOI: 10.1073/pnas.2313148120 -
F1000Research 2018The ichthyoses are a heterogeneous group of skin diseases characterized by localized or generalized scaling or both. Other common manifestations include palmoplantar... (Review)
Review
The ichthyoses are a heterogeneous group of skin diseases characterized by localized or generalized scaling or both. Other common manifestations include palmoplantar keratoderma, erythroderma, recurrent infections, and hypohidrosis. Abnormal barrier function is a cardinal feature of the ichthyoses, which results in compensatory hyperproliferation and transepidermal water loss. Barrier function is maintained primarily by the stratum corneum, which is composed of cornified cells surrounded by a corneocyte lipid envelope and intercellular lipid layers. The lipid components are composed primarily of ceramides. Human genetics has advanced our understanding of the role of the epidermal lipid barrier, and a series of discoveries in animals and humans revealed mutations in novel genes causing disorders of keratinization. Recently, next-generation sequencing has further expanded our knowledge, identifying novel mutations that disrupt the ceramide pathway and result in disorders of keratinization. This review focuses on new findings in ichthyoses caused by mutations involving lipid synthesis or function or both.
PubMed: 30002814
DOI: 10.12688/f1000research.14514.1 -
BMC Medical Genomics May 2023Congenital insensitivity to pain (CIP) is a rare autosomal recessive disorder characterized primarily by an inability to perceive physical pain from birth, resulting in...
BACKGROUND
Congenital insensitivity to pain (CIP) is a rare autosomal recessive disorder characterized primarily by an inability to perceive physical pain from birth, resulting in the accumulation of bruising, inflammation, and fractures that affect patient's life expectancy. CIP has different forms including CIP and CIPA. CIP with Anhidrosis (CIPA) is the most common type of CIP, which is caused mainly by mutations in NTRK1 and NGF genes, and is characterized by mental retardation and the inability to sweat (Anhidrosis). Because of high consanguinity rates in Palestine, this rare disease appears to have a higher frequency than in other communities. However, there were no systematic studies to address the genetic factors that cause CIP in the Palestinian community.
METHODS
In our study, we used Sanger and Whole exome sequencing to genotype members of five CIP-affected Palestinian families.
RESULTS
Our results confirm the presence of the founder c.1860-1861insT mutation in the NTRK1 gene of Palestinian Bedouin CIPA patients. Furthermore, one CIPA family carried a missense c.2170 G > A (G724 S) mutation in exon 16 of the NTRK1 gene. Finally, a novel nonsense c.901 A > T mutation (K301*) was detected in exon 7 of the SCN9A gene in CIP without anhidrosis family.
CONCLUSIONS
Our study revealed three mutations that cause CIP and CIPA in the Palestinian community, which can help in improving the process of diagnosis and genetic counseling and establishing protocols for the diagnosis and follow-up for the affected individuals. This is especially important given that early diagnosis and medical care interference can prevent unpleasant CIP and CIPA complications.
Topics: Humans; Pain Insensitivity, Congenital; Arabs; Hypohidrosis; Hereditary Sensory and Autonomic Neuropathies; Receptor, trkA; Mutation; NAV1.7 Voltage-Gated Sodium Channel
PubMed: 37248554
DOI: 10.1186/s12920-023-01544-5 -
Frontiers in Physiology 2021Ectodysplasin A (EDA) is a member of the tumor necrosis factor (TNF) family of ligands that was initially reported to induce the formation of various ectodermal... (Review)
Review
Ectodysplasin A (EDA) is a member of the tumor necrosis factor (TNF) family of ligands that was initially reported to induce the formation of various ectodermal derivatives during normal prenatal development. EDA exerts its biological activity as two splice variants, namely, EDA-A1 and EDA-A2. The former binds to the EDA receptor (EDAR), resulting in the recruitment of the intracellular EDAR-associated death domain (EDARADD) adapter protein and the activation of the NF-κB signaling pathway, while the latter binds to a different receptor, EDA2R, also known as X-linked ectodermal dysplasia receptor (XEDAR). Inactivation mutation of the EDA gene or the genes coding for its receptors can result in hypohidrosis ectodermal dysplasia (HED), a condition that is characterized by oligotrichosis, edentulosis or oligodontia, and oligohidrosis or anhidrosis. Recently, as a new liver factor, EDA is gradually known and endowed with some new functions. EDA levels were observed to be upregulated in several metabolic diseases, such as non-alcoholic fatty liver disease (NAFLD), obesity, and insulin resistance. In addition, EDA and its receptors have been implicated in tumor pathogenesis through the regulation of tumor cell proliferation, apoptosis, differentiation, and migration. Here, we first review the role of EDA and its two-receptor system in various signaling pathways and then discuss the physiological and pathological roles of EDA and its receptors.
PubMed: 34938205
DOI: 10.3389/fphys.2021.788411 -
Journal of Cardiothoracic and Vascular... Jun 2020THE RISK FACTORS, clinical manifestation, and preventive measures of Horner syndrome (HS) caused by internal jugular vein (IJV) catheterization were explored. Electronic... (Review)
Review
THE RISK FACTORS, clinical manifestation, and preventive measures of Horner syndrome (HS) caused by internal jugular vein (IJV) catheterization were explored. Electronic databases were searched to identify all case reports of HS caused by IJV catheterization. Two authors independently extracted literature characteristics, IJV catheterization method, clinical manifestations, and prognosis data. Twenty case reports (22 patients in total) were included, 18 of which were written in English and the other 2 in Chinese. Patients were between 19 months to 65 years old, and clinical manifestations included ptosis (n = 22), miosis (n = 21), anhidrosis (n = 8), enophthalmos (n = 3), and hoarseness (n = 1). Onset of HS manifestation ranged from a few hours to 19 days after the procedure. Eight patients with ptosis, 6 patients with miosis, and 1 patient with hoarseness recovered during follow-up. Of the 22 patients, 8 underwent more than 1 attempt of IJV catheterization. Six patients experienced accidental carotid artery puncture or hematoma formation during or after IJV catheterization. Ultrasound guidance was applied in 4 patients and anatomic landmark technique was used in the other 18 patients. The left IJV was catheterized in 3 patients, and the right IJV was catheterized in 19 patients. Repeated attempts of puncture, anatomic landmark technique, accidental carotid artery puncture, or hematoma formation may increase the possibility of HS. Ptosis and miosis are the most common manifestations of HS caused by IJV catheterization.
Topics: Carotid Arteries; Catheterization, Central Venous; Horner Syndrome; Humans; Jugular Veins; Ultrasonography
PubMed: 31350153
DOI: 10.1053/j.jvca.2019.06.031 -
Acta Dermato-venereologica Aug 2022
Topics: Alopecia; Humans; Hypohidrosis; Nail Diseases; Nails, Malformed; Propylthiouracil
PubMed: 35971830
DOI: 10.2340/actadv.v102.2690