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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 -
Cureus Nov 2023Hereditary sensory and autonomic neuropathy type 4 (HSAN4), or congenital insensitivity to pain with anhidrosis (CIPA), is a rare autosomal recessive disorder caused by...
Hereditary sensory and autonomic neuropathy type 4 (HSAN4), or congenital insensitivity to pain with anhidrosis (CIPA), is a rare autosomal recessive disorder caused by mutations in the NTRK1 gene, resulting in pain insensitivity, anhidrosis, and temperature dysregulation. This report focuses on oral manifestations in an 11-year-old girl with CIPA, highlighting the need for early intervention and comprehensive care. The patient had a history of recurrent oral injuries and an unexplained fever, with a confirmed HSAN4 diagnosis through genetic analysis. Clinical features included pain insensitivity, anhidrosis, and intellectual disability. Dental history revealed emergency care, suboptimal oral hygiene, early tooth loss, and infections. Extra-oral examination showed nail-biting and injuries, while intra-oral assessment revealed ulcers and scars. Radiographic evaluation indicated mandibular alveolar bone thinning and periapical lesions in the lower incisors. This case emphasizes the complex challenges of CIPA, including pain insensitivity, recurring fever episodes, and self-inflicted injuries. Early diagnosis and specific dental care are vital to prevent orofacial trauma, necessitating a proactive interdisciplinary approach for comprehensive care.
PubMed: 38058353
DOI: 10.7759/cureus.48294 -
Cureus Oct 2023Ectodermal dysplasia (ED) is a rare genetic disorder that affects the developmental disturbance of ectoderm-derived tissues, organs, and accessory appendages, i.e. skin,...
Ectodermal dysplasia (ED) is a rare genetic disorder that affects the developmental disturbance of ectoderm-derived tissues, organs, and accessory appendages, i.e. skin, hair, tooth, nail, and sweat glands. ED has two types hypohidrotic or anhidrotic ectodermal dysplasia and hidrotic ectodermal dysplasia. We report this case of classical hypohidrotic ectodermal dysplasia (HED) with clubbing. The association of clubbing with HED is still rare. This case report aims to discuss the etiology, clinical manifestations, and management of ectodermal dysplasia. A multidisciplinary approach is required including dentists, nutritionists, dermatologists, and physicians to manage ectodermal dysplasia.
PubMed: 37927739
DOI: 10.7759/cureus.46530 -
Cureus Sep 2023Horner's syndrome (HS) is a rare complication of thyroidectomy caused by damage to the oculosympathetic nerves. This article reports the case of a 29-year-old woman...
Horner's syndrome (HS) is a rare complication of thyroidectomy caused by damage to the oculosympathetic nerves. This article reports the case of a 29-year-old woman referred to the clinic with a newly diagnosed papillary thyroid carcinoma (PTC). Ultrasound studies were concerning for multiple thyroid nodules and an enlarged lymph node, confirmed by a computed tomography (CT) scan. Cytology results of fine needle aspiration (FNA) diagnostic for PTC showed tumors in the thyroid tissue and lymph node. The patient underwent a thyroidectomy and woke up with right-sided ptosis and miosis. Clinical follow-up revealed subjective ipsilateral anhidrosis. She also developed a low parathyroid hormone level and dysphonia, albeit they resolved after months. The patient still exhibits HS eight months after surgery. This paper reviews the literature and attempts to establish the most probable causal factor while providing implications for surgical teams to minimize HS occurrence in future thyroid surgeries.
PubMed: 37876407
DOI: 10.7759/cureus.45825 -
Acta Neurologica Taiwanica Sep 2023Ross syndrome is a rare disorder of unknown etiology, characterized by the triad of segmental anhidrosis, tonic pupil, and areflexia/hyporeflexia. Ross syndrome is...
Ross syndrome is a rare disorder of unknown etiology, characterized by the triad of segmental anhidrosis, tonic pupil, and areflexia/hyporeflexia. Ross syndrome is thought to be a limited and selective ganglioneuropathy. Its etiology has not been fully elucidated. Autonomic findings may also accompany. We wanted to present our 25-year-old patient who was diagnosed with Ross syndrome and presented with complaints of inability to sweat, heat intolerance, headache, diarrhea and chronic cough. Keyword: cough, tonic pupil, anhidrosis, compensatory.
Topics: Humans; Adult; Tonic Pupil; Hypohidrosis; Cough; Pupil Disorders; Adie Syndrome; Reflex, Abnormal
PubMed: 37674425
DOI: No ID Found -
Medicina (Kaunas, Lithuania) Aug 2023: Sensory ganglionopathy is a rare neurological disorder caused by degeneration of the neurons composing the dorsal root ganglia. It manifests as various sensory...
: Sensory ganglionopathy is a rare neurological disorder caused by degeneration of the neurons composing the dorsal root ganglia. It manifests as various sensory disturbances in the trunk, proximal limbs, face, or mouth in a patchy and asymmetrical pattern. Harlequin syndrome is characterized by unilateral flushing and sweating of the face, neck, and upper chest, concurrent with contralateral anhidrosis. Here, we present and discuss a clinical case of sarcoidosis-associated ganglionopathy and Harlequin syndrome. : A 31-year-old woman complained of burning pain in the right side of the upper chest and the feet. She also experienced episodes of intense flushing and sweating on the right side of her face, neck, and upper chest. Three years before these symptoms began, the patient was diagnosed with pulmonary sarcoidosis. On neurological examination, sensory disturbances were present. In the trunk, the patient reported pronounced hyperalgesia and allodynia in the upper part of the right chest and some patches on the right side of the upper back. In the extremities, hypoalgesia in the tips of the fingers and hyperalgesia in the feet were noted. An extensive diagnostic workup was performed to eliminate other possible causes of these disorders. A broad range of possible metabolic, immunological, and structural causes were ruled out. Thus, the final clinical diagnosis of sarcoidosis-induced sensory ganglionopathy, small-fiber neuropathy, and Harlequin syndrome was made. Initially, the patient was treated with pregabalin and amitriptyline, but the effect was inadequate for the ganglionopathy-induced pain. Therefore, therapeutic plasma exchange as an immune-modulating treatment was selected, leading to partial pain relief. : This case report demonstrates the possible autoimmune origin of both sensory ganglionopathy and Harlequin syndrome. It suggests that an autoimmune etiology for these disorders should be considered and the diagnostic workup should include screening for the most common autoimmune conditions.
Topics: Humans; Female; Adult; Hypohidrosis; Hyperalgesia; Sarcoidosis; Pain; Fingers
PubMed: 37629785
DOI: 10.3390/medicina59081495 -
Clinical, Cosmetic and Investigational... 2023Ectodermal dysplasia (ED) is an inherited disorder that affects the ectoderm of a developing embryo and impacts structures that originate from it. It typically presents...
Ectodermal dysplasia (ED) is an inherited disorder that affects the ectoderm of a developing embryo and impacts structures that originate from it. It typically presents as a triad of missing teeth (anodontia/hypodontia), sparse hair (atrichosis/hypotrichosis), and lack of sweat glands (hypohidrosis), often accompanied by nail dystrophy and palmoplantar hyperkeratosis. There are two main types of this condition: X-linked anhidrotic or hypohidrotic and hidrotic (autosomal type). The oral manifestation of ED may include anodontia or hypodontia, with or without cleft lip and palate. Tooth loss leads to a decrease in the height of the alveolar ridges, resulting in a reduction of the vertical dimension of the lower face, disappearance of the vermilion border, and prominent lips. As a result, the affected person's face may resemble that of an elderly individual. The current case report aims to illustrate the prosthodontic rehabilitation of 16-year-old male patient with ectodermal dysplasia and complete anodontia, visiting Dentistry Teaching Hospital, Kabul, Afghanistan. Fortunately, this patient was acceptably managed with the collaboration of several disciplines.
PubMed: 37576744
DOI: 10.2147/CCIDE.S419939 -
Skin Health and Disease Aug 2023Acquired idiopathic generalised anhidrosis (AIGA) is a rare disorder that is characterised by sudden onset generalised absence of sweating without any dermatological,...
Acquired idiopathic generalised anhidrosis (AIGA) is a rare disorder that is characterised by sudden onset generalised absence of sweating without any dermatological, neurological or sweat gland abnormalities. AIGA predominately affects young males, mostly involving patients of Asian descent. There have been approximately 100 reported cases worldwide, most of which were reported in Japan. In Singapore, it is rarely seen with one case series on 15 cases of AIGA reported in a 2014 study. Here, we present a case of AIGA who responded well to conservative management with sweating activity.
PubMed: 37538324
DOI: 10.1002/ski2.242 -
JID Innovations : Skin Science From... Jul 2023Sweat maintains systemic homeostasis in humans. Although sweating disorders may cause multifaceted health problems, therapeutic options for sweat disorders have not yet...
Sweat maintains systemic homeostasis in humans. Although sweating disorders may cause multifaceted health problems, therapeutic options for sweat disorders have not yet been established. To gain new insight into the mechanism underlying the regulation of perspiration, we compared eccrine sweat gland transcriptomes from hidrotic and anhidrotic lesions from patients with anhidrosis and found out that olfactory receptors were expressed differentially in anhidrotic and hidrotic eccrine sweat glands. We then confirmed OR51A7 and OR51E2 expression in human eccrine sweat glands by in situ hybridization and immunohistochemistry. An alkaline phosphatase-TGFα shedding assay revealed that β-ionone activates G-proteins through OR51A7 or OR51E2. The effect of topically applied β-ionone on sweating was examined with the quantitative sudomotor axon reflex test, which showed that responses to β-ionone differed between sexes. Topical β-ionone attenuated female sweating and augmented male sweating. Taken together, this study suggests that olfactory receptors expressed in eccrine sweat glands may regulate sweating in response to odorous ligands on the basis of sex. These unexpected results indicate that olfactory receptors may modulate sweating and that olfactory receptor modulators may contribute to the management of sweat disorders.
PubMed: 37533582
DOI: 10.1016/j.xjidi.2023.100196