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Congenital insensitivity to pain associated with mutation: Two case reports and a literature review.Frontiers in Genetics 2023is a newly discovered gene responsible for congenital insensitivity to pain (CIP). Its clinical manifestations are various and not widely known. The clinical data of...
is a newly discovered gene responsible for congenital insensitivity to pain (CIP). Its clinical manifestations are various and not widely known. The clinical data of two infants diagnosed with CIP associated with mutation were collected. A literature review was performed, and the clinical characteristics of 20 cases diagnosed with a mutation of were summarized and analyzed. Two patients had pain insensitivity, tongue and lip defects, and corneal ulcers. The genomic analysis results showed that variants of were detected in the two families. The case 1 patient carried heterozygous variations of c.682+1G > A and c.502C > T (p.R168C), which were inherited from her father and mother, respectively. We enrolled 22 patients diagnosed with CIP through a literature review together with our cases. There were 16 male (72.7%) and 6 female (27.3%) patients. The age of onset ranged from 6 months to 57 years. The prevalence of clinic manifestation was 14 cases with insensitivity to pain (63.6%), 19 cases with self-mutilation behaviors (86.4%), 11 cases with tongue and lip defects (50%), 5 cases with mid-facial lesions (22.7%), 6 cases with distal phalanx injury (27.3%), 11 cases of recurrent infection (50%), 3 cases (13.6%) with anhidrosis, and 5 cases (22.7%) with global developmental delay. The prevalence of ocular symptoms was 11 cases (50%) with reduced tear secretion, 6 cases (27.3%) with decreased corneal sensitivity, 7 cases (31.8%) with disappeared corneal reflexes, 5.5 cases (25%, 0.5 indicated a single eye) with corneal opacity, 5 cases (22.7%) with corneal ulceration, and 1 case (4.5%) with a corneal scar. The syndrome caused by mutation is a clinically distinct and diagnosable disease that requires joint multidisciplinary management to control the development of the disease and minimize the occurrence of complications.
PubMed: 37021010
DOI: 10.3389/fgene.2023.1139161 -
Frontiers in Pediatrics 2023The clinical characteristics of Ulnar-mammary syndrome (UMS) caused by mutations in (T-Box transcription factor 3) were studied and the correlation between genotype and...
OBJECTIVE
The clinical characteristics of Ulnar-mammary syndrome (UMS) caused by mutations in (T-Box transcription factor 3) were studied and the correlation between genotype and clinical phenotype were analyzed to improve awareness and early diagnosis of the disease.
METHODS
The clinical data of a boy aged 13 years and 5 months with left forearm deformity and growth retardation as the main features were analyzed. Genomic exon detection was performed, and the results were verified by Sanger sequencing. Simultaneously, we performed literature review to analyze the correlation between clinical phenotypes and genotypes.
RESULTS
The clinical manifestations in the child were short stature, ulnar hypoplasia of the forearm, hypohidrosis, retracted nipple, micropenis, and cryptorchidism. Laboratory examination revealed hyperthyroidism, growth hormone deficiency, and hypogonadotropic hypogonadism. Imaging results displayed delayed bone age, small pituitary gland, and persistence of Rathke's cleft cyst. The results of the exome sequencing revealed the deletion of AGA at positions 1121-1,124 of , which resulted in a frameshift mutation (c.1121-1124del AGAG; pGlu374fs). According to the American College of Medical Genetics (ACMG) assessment, the mutation is a pathogenic variant. A definitive diagnosis of UMS was made on the basis of the clinical phenotype of the patient. The Chinese and English literature were reviewed to analyze the correlation between genotype and clinical phenotype.
CONCLUSION
UMS is a rare hereditary disease caused by mutations in . There is significant clinical heterogeneity associated with the variants of this gene. To our knowledge, this mutation site in has been reported for the first time, thereby expanding the mutation spectrum of this gene.
PubMed: 36937985
DOI: 10.3389/fped.2023.1052931 -
International Journal of Molecular... Feb 2023Sweat plays a critical role in human body, including thermoregulation and the maintenance of the skin environment and health. Hyperhidrosis and anhidrosis are caused by...
Sweat plays a critical role in human body, including thermoregulation and the maintenance of the skin environment and health. Hyperhidrosis and anhidrosis are caused by abnormalities in sweat secretion, resulting in severe skin conditions (pruritus and erythema). Bioactive peptide and pituitary adenylate cyclase-activating polypeptide (PACAP) was isolated and identified to activate adenylate cyclase in pituitary cells. Recently, it was reported that PACAP increases sweat secretion via PAC1R in mice and promotes the translocation of AQP5 to the cell membrane through increasing intracellular [Ca] via PAC1R in NCL-SG3 cells. However, intracellular signaling mechanisms by PACAP are poorly clarified. Here, we used PAC1R knockout (KO) mice and wild-type (WT) mice to observe changes in AQP5 localization and gene expression in sweat glands by PACAP treatment. Immunohistochemistry revealed that PACAP promoted the translocation of AQP5 to the lumen side in the eccrine gland via PAC1R. Furthermore, PACAP up-regulated the expression of genes (, , ) involved in sweat secretion in WT mice. Moreover, PACAP treatment was found to down-regulate the gene expression in PAC1R KO mice. These genes were found to be involved in multiple pathways related to sweating. Our data provide a solid basis for future research initiatives in order to develop new therapies to treat sweating disorders.
Topics: Mice; Humans; Animals; Pituitary Adenylate Cyclase-Activating Polypeptide; Sweat; Sweating; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; Pituitary Gland
PubMed: 36902003
DOI: 10.3390/ijms24054572 -
European Journal of Medical Research Feb 2023Drug repurposing refers to the application of existing drugs to new therapeutic indications. As phenotypic indicators of human drug response, drug side effects may... (Observational Study)
Observational Study
BACKGROUND
Drug repurposing refers to the application of existing drugs to new therapeutic indications. As phenotypic indicators of human drug response, drug side effects may provide direct signals and unique opportunities for drug repurposing.
OBJECTIVES
We aimed to identify drugs frequently associated with hypohidrosis or anhidrosis adverse reactions (that is, the opposite condition of hyperhidrosis) from the pharmacovigilance database, which could be potential candidates as anti-hyperhidrosis treatment agents.
METHODS
In this observational, retrospective, pharmacovigilance study, adverse event reports of hypohidrosis or anhidrosis in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) were assessed between January 2004 and December 2021 using reporting odds ratio (ROR) estimates and categorized by the World Health Organization Anatomical Therapeutic Chemical (ATC) classification code. The onset time of drug-associated hypohidrosis or anhidrosis was also examined.
RESULTS
There were 540 reports of 192 drugs with suspected drug-associated hypohidrosis or anhidrosis in the FAERS database, of which 39 drugs were found to have statistically significant signals. Nervous system drugs were most frequently reported (187 cases, 55.82%), followed by alimentary tract and metabolism drugs (35 cases, 10.45%), genitourinary system and sex hormones (28 cases, 8.36%), and dermatologicals (22 cases, 6.57%). The top 3 drug subclasses were antiepileptics, drugs for urinary frequency and incontinence, and antidepressants. Taking disproportionality signals, pharmacological characteristics of drugs and appropriate onset time into consideration, the main putative drugs for hyperhidrosis were glycopyrronium, solifenacin, oxybutynin, and botulinum toxin type A. Other drugs, such as topiramate, zonisamide, agalsidase beta, finasteride, metformin, lamotrigine, citalopram, ciprofloxacin, bupropion, duloxetine, aripiprazole, prednisolone, and risperidone need more investigation.
CONCLUSIONS
Several candidate agents among hypohidrosis or anhidrosis-related drugs were identified that may be redirected for diminishing sweat production. There are affirmative data for some candidate drugs, and the remaining proposed candidate drugs without already known sweat reduction mechanisms of action should be further explored.
Topics: Humans; United States; Hypohidrosis; Pharmaceutical Preparations; Pharmacovigilance; Drug Repositioning; Retrospective Studies; Hyperhidrosis; Databases, Factual
PubMed: 36829251
DOI: 10.1186/s40001-023-01048-z -
Tidsskrift For Den Norske Laegeforening... Feb 2023A previously healthy male patient in his fifties presented with subacute onset of severe, diffuse dysautonomia with orthostatic hypotension as the main symptom. A...
BACKGROUND
A previously healthy male patient in his fifties presented with subacute onset of severe, diffuse dysautonomia with orthostatic hypotension as the main symptom. A lengthy interdisciplinary workup revealed a rare condition.
CASE PRESENTATION
Over the course of a year, the patient was twice admitted to the local department of internal medicine because of severe hypotension. Testing showed severe orthostatic hypotension with normal cardiac function tests and no apparent underlying cause. On referral to neurological examination, symptoms of a broader autonomic dysfunction were discovered, with symptoms of xerostomia, irregular bowel habits, anhidrosis and erectile dysfunction. The neurological examination was normal, except for bilateral mydriatic pupils. The patient was tested for ganglionic acetylcholine receptor (gAChR) antibodies. A strong positive result confirmed the diagnosis of autoimmune autonomic ganglionopathy. There were no signs of underlying malignancy. The patient received induction treatment with intravenous immunoglobulin and later maintenance treatment with rituximab, resulting in significant clinical improvement.
INTERPRETATION
Autoimmune autonomic ganglionopathy is a rare but likely underdiagnosed condition, which may cause limited or widespread autonomic failure. Approximately half of the patients have ganglionic acetylcholine receptor antibodies in serum. It is important to diagnose the condition as it can cause high morbidity and mortality, but responds to immunotherapy.
Topics: Humans; Male; Autoantibodies; Autoimmune Diseases; Ganglia, Autonomic; Hypotension, Orthostatic; Receptors, Cholinergic; Syncope; Vertigo; Middle Aged
PubMed: 36811431
DOI: 10.4045/tidsskr.22.0092 -
Molecular Therapy : the Journal of the... Apr 2023Fabry disease (FD), a lysosomal storage disorder, is caused by defective α-galactosidase (GLA) activity, which results in the accumulation of globotriaosylceramide...
Fabry disease (FD), a lysosomal storage disorder, is caused by defective α-galactosidase (GLA) activity, which results in the accumulation of globotriaosylceramide (Gb3) in endothelial cells and leads to life-threatening complications such as left ventricular hypertrophy (LVH), renal failure, and stroke. Enzyme replacement therapy (ERT) results in Gb3 clearance; however, because of a short half-life in the body and the high immunogenicity of FD patients, ERT has a limited therapeutic effect, particularly in patients with late-onset disease or progressive complications. Because vascular endothelial cells (VECs) derived from FD-induced pluripotent stem cells display increased thrombospondin-1 (TSP1) expression and enhanced SMAD2 signaling, we screened for chemical compounds that could downregulate TSP1 and SMAD2 signaling. Fasudil reduced the levels of p-SMAD2 and TSP1 in FD-VECs and increased the expression of angiogenic factors. Furthermore, fasudil downregulated the endothelial-to-mesenchymal transition (EndMT) and mitochondrial function of FD-VECs. Oral administration of fasudil to FD mice alleviated several FD phenotypes, including LVH, renal fibrosis, anhidrosis, and heat insensitivity. Our findings demonstrate that fasudil is a novel candidate for FD therapy.
Topics: Animals; Mice; Fabry Disease; Endothelial Cells; alpha-Galactosidase; Phenotype; Enzyme Replacement Therapy
PubMed: 36755495
DOI: 10.1016/j.ymthe.2023.02.003 -
Annals of Cardiac Anaesthesia 2023The use of ECPELLA in patients with severe lung disease may result in an unfavorable phenomenon of differential hypoxia. The simultaneous evaluation of three arterial...
The use of ECPELLA in patients with severe lung disease may result in an unfavorable phenomenon of differential hypoxia. The simultaneous evaluation of three arterial blood samples from different arterial line (right radial artery, left radial artery, ECMO arterial line) in patients at risk of Harlequin syndrome (also called differential hypoxemia (DH)) can localize the "mixing cloud" along the aorta. Focusing the attention on the "mixing cloud" position instead of on isolated flows of Veno-Arterial Extracorporeal Membrane Oxygenation (VA ECMO) and Impella CP makes the decision making easier about how to modify MCSs flows according to the clinical context. Herein, we present two cases in which ECPELLA configuration was used to treat a cardiogenic shock condition and how the ECPELLA-induced hypoxia was managed.
Topics: Humans; Autonomic Nervous System Diseases; Hypohidrosis; Aorta; Hypoxia
PubMed: 36722597
DOI: 10.4103/aca.aca_176_21 -
Journal of Clinical Medicine Jan 2023Horner’s syndrome (HS), caused by lesions of the 3-neuron oculosympathetic nerve pathway (ONP), includes the triad: blepharoptosis, miosis and anhidrosis (ipsilateral... (Review)
Review
Horner’s syndrome (HS), caused by lesions of the 3-neuron oculosympathetic nerve pathway (ONP), includes the triad: blepharoptosis, miosis and anhidrosis (ipsilateral with ONP damage). Thyroid−related HS represents an unusual entity underling thyroid nodules/goiter/cancer−HS (T-HS), and post-thyroidectomy HS (Tx-HS). We aim to overview Tx-HS. This is a narrative review. We revised PubMed published, full-length, English papers from inception to November 2022. Additionally, we introduced data on post-thyroidectomy lymphocele/chylous leakage (Tx-L), and introduced a new pediatric case with both Tx-HS and Tx-L. Tx-HS: the level of statistical evidence varies from isolated case reports, studies analyzing the large panel of post-thyroidectomy complications reporting HS among the rarest side effects (as opposite to hypocalcemia), or different series of patients with HS due to various disorders, including T-HS/Tx-HS. Tx-HS is related to benign or malignant thyroid conditions, regardless the type of surgery. A pre-operatory rate of T-HS of 0.14%; a post-operatory rate of Tx-HS between 0.03% and 5% (mostly, 0.2%) are identified; a possible higher risk on endoscopic rather than open procedure is described. Incomplete HS forms, and pediatric onset are identified, too; the earliest identification is after 2 h since intervention. A progressive remission is expected in most cases within the first 2−6 months to one year. The management is mostly conservative; some used glucocorticoids and neurotrophic agents. One major pitfall is an additional contributor factor like a local compression due to post-operatory collections (hematoma, cysts, fistula, Tx-L) and their correction improves the outcome. The prognostic probably depends on the severity of cervical sympathetic chain (CSC) lesions: indirect, mild injury due to local compressive masses, intra-operatory damage of CSC like ischemia and stretching of CSC by the retractor associate HS recovery, while CSC section is irreversible. Other iatrogenic contributors to HS are: intra-operatory manipulation of parathyroid glands, thyroid microwave/radiofrequency ablation, and high-intensity focused ultrasound, and percutaneous ethanol injection into thyroid nodules. Tx-L, rarely reported (mostly <0.5%, except for a ratio of 8.3% in one study), correlates with extended surgery, especially lateral/central neck dissection, and the presence of congenitally—aberrant lymphatic duct; it is, also, described after endoscopic procedures and chest-breast approach; it starts within days after surgery. Typically low-fat diet (even fasting and parental nutrition) and tube drainage are useful (as part of conservative management); some used octreotide, local sealing solutions like hypertonic glucose, Viscum album extract, n-Butyl-2-cyanoacrylate. Re-intervention is required in severe cases due to the risk of lymphorrhoea and chylothorax. Early identification of Tx-HS and Tx-L improves the outcome. Some iatrogenic complications are inevitable and a multifactorial model of prediction is still required, also taking into consideration standardized operatory procedures, skillful intra-operatory manipulation, and close post-operatory follow-up of the patients, especially during modern era when thyroid surgery registered a massive progress allowing an early discharge of the patients.
PubMed: 36675400
DOI: 10.3390/jcm12020474