Atypical Clinical Manifestations Research Articles

Paraproteinemic neuropathies

Paraproteinemic polyneuropathies (PPN) occur generally infrequently and arise from diseases, associated with formation and accumulation of a pathological protein, commonly known as paraprotein, which is typically an immunoglobulin or its free light chain. Such diseases include the following: monoclonal gammopathy of undetermined significance, multiple myeloma, Waldenström’s macroglobulinemia, AL amyloidosis, POEMS syndrome, etc. Diagnosis of PPN is challenging due to nonspecific, indistinct or atypical clinical manifestation, and it is necessary to apply specialized laboratory methods, including immunochemical analysis of blood and urine. Moreover, medications can cause symptoms of polyneuropathy themselves. Thus, it is important to suspect the first symptoms of the disease in time, determine the mechanism of damage to nerve fibers, carry out differential diagnosis and initiate therapy targeting the suppression of pathological protein synthesis.

#2889 Multiple renal tumors as an atypical clinical manifestation of granulomatosis with polyangiitis

Abstract Background and Aims Granulomatosis with polyangiitis (GPA) is a systemic small- vessel vasculitis associated with antineutrophilic cytoplasmic antibody (ANCA), in which kidney involvement often occurs. In some cases the course of vasculitis with kidney involvement is atypical, what complicates the diagnostic process and makes appropriate treatment difficult. Finding nodular masses in the kidneys always causes an oncological concern, while in the differential diagnosis a systemic vasculitis is rarely taken into account, what may lead to an unnecessary nephrectomy. Method We present a case of granulomatosis with polyangiitis (GPA) who presented with multiple tumors in the kidneys and adrenal gland. Results 29-year-old man experienced a sudden disease onset, at the age of 18 years, when due to peripheral oedema, nephrotic grade proteinuria (13.7 g/24 h), hematuria and presence of renal failure markers (serum creatinine 3.4 mg/dL), he was admitted to hospital. A suggestion of a rapidly progressive glomerulonephritis (RPGN) was put forward and a renal biopsy was performed (in the histopathological examination of the kidney, pauci-immune crescentic necrotizing glomerulonephritis was revealed). A treatment with plasmaphereses, high glucocorticosteroid doses and cyclophosphamide pulses was instituted. Haemodialysis therapy was also applied temporarily. ANCA and anti-glomerular basement membrane (GBM) antibodies were determined to give negative results. As a result of the remission-inducing treatment, an improvement of the renal function was obtained (serum creatinine 1.6-1.9 mg/dL). In spite of the remission-maintaining treatment with mycophenolate mofetil (MMF) and oral prednisone, after 10 years again a dramatic renal function impairment occurred, with a necessity of institution of a long-term haemodialysis therapy. Furthermore, on abdominal ultrasound examination multiple focal lesions were found in both kidneys, which rendered a kidney transplantation procedure in the patient impossible. In order to extend the diagnostic procedures, a magnetic resonance imaging (MRI) of the abdominal cavity without contrast agent administration was carried out (in both kidneys disseminated focal lesions were described: non-homogeneous, with moderately enhanced signal on T2-weighted images in the central part, without signs of water diffusion restriction; in the left kidney, of 23 x 22 mm and 19 x 15 mm dimensions; in the right kidney, of 30 x 32 mm, 26 x 22 mm and 22 x 18 mm dimensions. The picture of the lesions was unspecific and atypical. In the differential diagnosis granulomas could not have been ruled out, while disseminated proliferative lesions were less likely. Besides that, in both kidneys cysts of up to 7 mm diameters were present. In the lateral limb of the left adrenal gland a focal lesion was visible, of 23 x 14 mm dimensions, of a structure identical to that of the foci in both kidneys). On high-resolution computed tomography (HRCT) of the chest at the same time, small ground glass areas were found in the lungs. On positron emission tomography/computed tomography (PET/CT) no changes were visualised, suggesting presence of a metabolically active proliferative process. Tests for ANCA, antinuclear antibodies (ANA), anti- double-stranded DNA (dsDNA) antibodies, anti- GBM antibodies were again performed and gave negative results. He was diagnosed with granulomatosis with polyangiitis without ANCA and treated with corticosteroid and intravenous rituximab (4x 787 mg). Three months later, follow-up showed reduced mass lesions in the kidney and adrenal gland by MRI. Conclusion The case highlights the atypical clinical presentation of vasculitis and the significance of considering this possibility in differential diagnosis when confronting mass lesions present in the kidney.

Delayed infected hematoma in retrosternal area following total thyroidectomy: a case report

Introduction and importance: Postoperative neck hematoma (PNH), a rare complication following thyroidectomy, occurs in only 1.1%-3.15% of cases and can lead to life-threatening outcomes. More rarely, delayed PNHs with atypical clinical manifestations and positions have not yet been reported. Early identification and immediate medical intervention are of utmost importance in such cases. Case presentation: The authors represented a patient with thyroid cancer adherent to the trachea, who underwent post-thyroidectomy, experienced delayed PNH in the retrosternal region and was infected by respiratory pathogens. Meanwhile, the patient developed recurrent laryngeal nerve (RLN) paralysis after surgery. PNH was not identified in the clinical manifestations; instead, it was detected only through successive cervical ultrasound examinations. Clinical discussion: Although rare, PNH can lead to serious complications, especially delayed complications or those in atypical positions, without neck swelling. When simultaneously with RLN paralysis, the hematoma may be neglected. Therefore, early diagnosis and treatment are crucial. Conclusion: Clinicians should be vigilant of atypical PNH because neck swelling may be absent. Cervical ultrasonography is essential for diagnosis and can be performed multiple times. Cervical CT scans should be part of the routine procedure, while contrast-enhanced ultrasound can help detect active bleeding. Early postoperative antibiotics are recommended if the tumor is closely attached to the trachea.

Persistent Abdominal Pain with an Uncommon Presentation of Multiple Myeloma: A Case Study

Multiple myeloma (MM) is a widespread malignant condition characterized by the proliferation of transformed plasma cells in the bone marrow, disrupting its normal functions and infiltrating adjacent bone tissues. While typically confined to the bone marrow, in rare instances, patients may develop extramedullary disease. In these uncommon scenarios, the involvement of lymph nodes poses a diagnostic challenge for practitioners in their daily routines. This report details the case of a 49-year-old male experiencing chronic abdominal pain. A computed tomography (CT) scan revealed enlargement of retroperitoneal and mesenteric lymph nodes. Biopsies confirmed a plasma cell infiltrate positive for CD138 and kappa light chain, leading to the diagnosis of multiple myeloma with extramedullary localization in lymph nodes. Our case underscores the rare presentation of extramedullary involvement in multiple myeloma, characterized by an atypical clinical manifestation.

Navigating the diagnostic maze: A case presentation of C1q vasculitis mimicking hypocomplementemic urticarial vasculitis in a patient with systemic lupus erythematosus.

In rare instances, patients with SLE may exhibit atypical clinical manifestations, such as Hypocomplementemic Urticarial Vasculitis, which can pose diagnostic challenges. Here, we present a case report of a 28-year-old female with a history of SLE with lupus nephritis clase IV who developed HUV-like symptoms, ultimately leading to a diagnosis of C1q Vasculitis. This case underscores the importance of considering C1q Vasculitis in SLE patients presenting with HUV-like features and highlights Rituximab as a promising therapeutic option for managing this rare condition.

MR Imaging of Typical Ovarian Hemangioma: A Case Report

Background: Ovarian hemangioma is an extremely rare tumor with atypical clinical manifestations, often discovered incidentally during autopsy or surgery. Approximately 60 cases have been reported in the past, but no more than 10 cases have been investigated by MRI and ultrasound (US). Case Presentation: ln this paper, we reported a 51-year-old female patient with Ovarian Hemangioma who had no symptoms of abdominal pain, abnormal vaginal bleeding or discharge, or any other discomfort. Laboratory tests revealed an elevated serum carbohydrate antigen (CA125) of 48.99U/ml (reference range: 0-35U/ml). Multiparametric 3.0T magnetic resonance imaging (MRI) showed a cystic solid mass with a clear boundary and regular shape in the left ovarian area and minimal ascites in the abdominal cavity. The histological examination of the mass confirmed an ovarian hemangioma. Conclusion: The MRI findings of ovarian hemangiomas are highly similar to those observed in hepatic hemangiomas, emphasizing the distinctive radiological characteristics specific to this condition in the ovary. This paper presents an overview of the typical MRI findings associated with ovarian hemangioma, which holds great importance for accurate diagnosis and effective treatment.

FLAMES overlaying anti-N-methyl-D-aspartate receptor encephalitis: a case report and literature review

BackgroundIn recent years, simultaneous or sequential occurrence of MOG antibody disease and anti-NMDAR encephalitis in the same patient has been reported with increasing frequency. Scholars refer to the overlapping occurrence of these two disorders as MOG antibody disease and anti-NMDAR encephalitis overlap syndrome (MNOS). Cortical T2-weighted fluid-attenuated inversion recovery (FLAIR) -hyperintense lesions in anti-MOG-associated encephalitis with seizures (FLAMES) is a rare clinical phenotype of MOGAD in which cortical FLAIR high-signal lesions are unilateral, with little spread to the cortex and meninges bilaterally. Although cases of FLAMES have been consistently reported. However, to our knowledge, such cases of FLAMES combined with NMDARE are rare.Case presentationHere, we describe a case of FLAMES combined with anti-NMDARE. The patient was a young male, 29 years old, admitted to our hospital with isolated seizures, whose MRI showed unilateral thalamic and bilateral frontal and parietal leptomeningeal involvement. Since we were unaware of the possibility of bilateral meningo-cortical MOGAD manifestations, the case was initially diagnosed as viral encephalitis and was given antiviral therapy. The diagnosis was not clarified until anti-NMDAR-IgG and MOG-IgG positivity was detected in the cerebrospinal fluid and serum. The patient was then treated with high-dose corticosteroids and his symptoms responded well to the steroids. Therefore, this case expands the clinical spectrum of MNOS overlap syndrome. In addition, we describe the clinical features of MNOS by summarizing the existing literature and exploring the possible mechanisms of its immune response.ConclusionsOur case serves as a reminder to clinicians that when patients present with atypical clinical manifestations such as seizures, consideration should be given to MNOS and conduct testing for various relevant autoantibodies (including MOG abs) and viruses in both serum and cerebrospinal fluid, as it is easy to misdiagnose the disease as other CNS diseases, such as viral meningoencephalitis. This syndrome exhibits a high responsiveness to steroids, highlighting the critical importance of recognizing the clinical and neuroimaging features of this overlap syndrome for prompt diagnosis and treatment. Furthermore, it enriches the disease spectrum of MNOS.

Generalized edema as an atypical clinical manifestation in a pedia-tric patient with celiac disease

Generalized edema as an atypical clinical manifestation in a pedia-tric patient with celiac disease

Primary Paraganglioma of the Prostate: A Systematic Review of the Literature for A Rare Entity.

Paragangliomas of the urinary tract are exceptionally uncommon, and sporadic case reports of primary paraganglioma of the prostate have been reported in the literature. Systematic research in PubMed/Medline and Scopus databases concerning primary prostatic paraganglioma was performed by two independent investigators. This analysis included 25 adult males, with a mean age of 49.8 ± 22.4 years. 32% of included patients had a history of hypertension. Problems during urination (52%), blood loss (44%), either as hematuria or hemospermia, and catecholamine-related symptoms (36%) comprised the most frequently reported clinical manifestations. Digital rectal examination found a palpable nodule in 36% of patients, while prostatic specific antigen (PSA) was normal in all tested patients. Abdominal ultrasound (44%), computed tomography (44%) and magnetic resonance imaging (28%) helped to identify the primary lesion. 24-hour urine epinephrine, norepinephrine and vanillylmandelic acid (VMA) levels were elevated in 90%, 80% and 90% of included patients. Open surgical excision of the mass was performed in 40%, transurethral resection in 8%, open radical prostatectomy in 24%, transurethral resection of the prostate in 16% and robot-assisted radical prostatectomy in 4% of included patients. Due to atypical clinical manifestation and scarcity of prostatic paraganglioma, urologists should be aware of this extremely rare entity.

P1025 Analysis of the Clinical Characteristics of Elderly-onset Crohn's Disease

Abstract Background The prevalence of Crohn's disease in the elderly is increasing today. The purpose of this study was to analyze the clinical characteristics of elderly-onset patients with Crohn's disease and compare with non-elderly-onset adult patients. Methods All Crohn's disease patients with onset aged 60 years and older at our Inflammatory Bowel Disease Center in recently ten years were retrospectively included. The elderly were compared with adult patients aged 18-59 at the time of onset, who were matched according to diagnosis time and gender by a 1:3 ratio of propensity score matching. After matching, the clinical data were recorded and analyzed to compared between the two groups of patients. Results A total of 68 patients were included, including 17 patients in the elderly-onset group and 51 patients in the non-elderly-onset adult group. The mean age of diagnosis in the two groups was 30.3±8.7 years and 63.9±4.24 years, and the mean course of disease was 30.3 months and 63.9 months, respectively. According to the Montreal classification, most elderly patients presented with L3 (70.6%) and B1 (58.8%), no cases involving the upper digestive tract or multiple lesion sites, showed mild disease activity (76.5%). The elderly group had fewer intestinal complications and parenteral manifestations. The medication types of elderly are 5-aminosalicylates (52.9%), traditional immunosuppressive agents (45.6%) and enteral nutrition preparations (29.4%) being the more frequent types of medications used, and glucocorticoids and biologics being used less frequently. Exposure to two or more IBD medications was 31.4% and 52.9% in the non-elderly onset adult group versus the elderly onset group, respectively (p=0.110). During follow-up, symptoms such as diarrhea (11.8 vs 5.9%), abdominal pain (35.3% vs 17.6%) and weight loss (11.8% vs 3.9%) were more common in the elderly-onset group. Elderly patients had more hospitalizations on average (0.22 vs. 1.12). 40.7% of elderly patients underwent CD-related surgery during the duration of their disease, with 50.0% of patients undergoing reoperation. Conclusion Compared with non-elderly-onset adult patients, elderly-onset patients with Crohn's disease are more common in women, and the lesion mainly in the ileum and ilecolon; the disease behavior is mainly B1; nearly half of the patients have intestinal complications The elderly have atypical clinical manifestations, basically haven’t family history of IBD, take longer to diagnose, have more underlying diseases, more hospitalizations on average, and are more likely to have complications. They are more likely to receive conservative treatment, but with more frequent medication adjustments and a higher likelihood of undergoing CD-related surgery.

Carbon dot-based fluorescent probe for early diagnosis of pheochromocytoma through identification of circulating tumor cells

Pheochromocytoma (PCC), as a rare neuroendocrine tumor, is often missed or misdiagnosed because of its atypical clinical manifestations. To realize the early accurate diagnosis of PCC, we have selected circulating tumor cells (CTCs) with more complete biological information as biomarkers and developed a simple and novel fluorescence cytosensor. Octreotide-2,2′,2′′,2′’’- (1,4,7,10 -tetraazacyclododecane-1,4,7,10-tetrayl) tetraacetic acid (DOTA) modified magnetic Fe3O4 and signal amplification CDs@SiO2 nanospheres are prepared to capture and detect PCC-CTCs from peripheral blood via binding to the somatostatin receptor SSTR2 overexpressed on the surface of PCC cells. During the detection process, the target cells were separated and enriched by magnetic capture probes (Fe3O4-DOTA), and then signal probes (CDs@SiO2-DOTA) could also specifically bound to target cells to form the sandwich-like structure for fluorescence signal output. The proposed fluorescence cytosensor has revealed good sensitivity and selectivity for quantitative analysis of PCC-CTCs in the concentration of 5–1000 cells mL−1 with a LOD of 2 cells mL−1. More importantly, designed fluorescence cytosensor has shown good reliability and stability in complex serum samples. This strategy provides a new way for detection of PCC-CTCs.

Pityriasis Rubra Pilaris: An Uncommon Presentation

Human immunodeficiency virus (HIV) associated pityriasis rubra pilaris (PRP) or PRP Type VI is a distinctive entity reported in HIV patients. We report a patient with skin Type V (based on the Fitzpatrick scale), and HIV infection, presenting with an atypical clinical manifestation (non-acneiform), and with an uncommon distribution of this entity but characteristic histological findings of Type VI PRP. We review the clinical features, pathology and possible aetiology of this entity.

Tracheobronchial mucosal keratosis: A literature review of this rare disorder

BackgroundTracheobronchial mucosal keratosis (TBMK) is a rare airway disease that may cause refractory cough and airway stenosis. The characteristics of this disease remain unknown. In the present study, we describe this disorder based on a review of the current literature, emphasizing its diagnostic and therapeutic aspects. MethodsA comprehensive search of TBMK was performed in Medline, Google Scholar, Web of Science, Cochrane Library (UK), Embase, China National Knowledge Infrastructure (CNKI) (China), and Wan Fang Med Online (China). The following data were collected: patient characteristics, chest imaging findings, bronchoscopy, histopathologic findings, pathogen testing, treatment, and prognosis. ResultsAs of 2023, eighteen cases of TBMK have been reported. The main clinical manifestations were cough and expectoration. Chest imaging findings were non-specific. The main bronchoscopy findings were nodular protrusion of airway lumen and yellow-white purulent moss above the nodular lesion. The lesions were mainly located in the trachea and mainstem bronchus. The main pathological manifestations include keratinocytes or keratinocyte beads, squamous metaplasia, and mucosal inflammatory changes. The treatments that were administered include antibiotics, symptomatic treatment, and glucocorticoids. All methods were ineffective except for bronchoscopy-guided high-frequency electric knife and recombinant human epidermal growth factor treatment. ConclusionsTBMK is a rare respiratory disease with atypical clinical manifestations and chest computed tomography findings. Bronchoscopy revealed that nodular hyperplasia of the airway and purulent fur-covered lesions are typical manifestations. The final diagnosis needs to be confirmed by histopathological examination. There is a lack of effective treatment for this disease, and bronchoscopy-guided intervention therapy may be a candidate treatment.

Selective vulnerability of subcortical nuclei in atypical Alzheimer’s Disease

AbstractBackgroundRecent evidence suggests that sleep‐wake dysregulation in Alzheimer’s disease (AD) is an early event and parallels the tau accumulation in the arousal system spefically noted in the locus coeruleus (LC) as well as other subcortical nuclei as the Pedunculopontine Tegmental Nucleus (PPTg), Laterodorsal Tegmental Nucleus (LDTg), and the Dorsal Raphe (DR). We have previously demonstrated that the pattern of sleep‐wake dysfunction is different among AD clinical variants. This existence of specific sleep‐wake profiles suggest differential degeneration patterns of the arousal system within differing AD presentations. This study continues this investigation at the cellular/molecular level to uncover the selective vulnerability of subcortical structures to AD specific tau accumulation. That remains elusive to‐date.MethodHuman postmortem brainstem samples were sourced from the Neurodegenerative Disease Brain Bank (NDBB) at UCSF. 24 subjects were selected based on primary diagnosis, including 6 amnestic AD, 17 non‐amnestic AD (5 EOAD, 3 PCA, 5 lvPPA, 4 CBS) and 1 control. Paraffin blocks containing the areas of interest were cut into 8‐lm‐thick sections that underwent double‐labeled immunohistochemistry (IHC) and brightfield imaging. The images were then overlayed to created mutlidimentaional maps and neurons were classified in 4 subgroups: (1) positive for the neurotransmitter of interest (NEU‐positive), (2) bearing hyperphosphorylated tau neuronal cytoplasmic inclusions (tau‐positive), (3) positive for the neurotransmitter of interest and bearing tau‐positive (NEU‐positive/tau‐positive colocalized neurons), and (4) negative for NEU and tau.ResultIn the LC, lvPPA had the highest had the highest percentage of tau postive neurons (40%), followed by amnestic AD (31.1%), PCA (29.3%), EOAD (27.1%), and finally CBS (24.3%). EOAD had the highest percentage of colocalized neurons (34.7%) as well as LOAD (31%) compared to PCA (0.02%), lvPPA (0.18%), CBS (0.09%).ConclusionMultidimensional quantitative analysis suggests differences in vulnerabliblity of sleep‐wake subcortical nuclei to AD, EOAD, PCA, lvPPA, and CBS. For instance the neuronal loss in EOAD was so extreme in the LC that few neurons remained to develop aggregates whereas in PCA, CBS, and lvPPA the high percentage of tau accumulation presents a neuropathological framework underlying atypical clinical manifestations and possible insight into therapeutic targets.

Hypophysitis In An Elderly Woman With COVID-19 - A Case Report

We report a case of an 87-year-old woman with hyperactive delirium about seven days after diarrhea. Serology for COVID-19, collected at the time of behavioral symptoms, was positive. She evolved with a decreased level of consciousness and normal neuroimaging and electroencephalogram tests. Endocrinological investigation found dysfunction of the hypothalamic-pituitary axis, with a good response to hormone replacement. In conclusion, this report emphasizes the importance of being alert to atypical clinical manifestations and unusual complications against the background of Covid-19.

Rare primary pulmonary mucosa-associated lymphoid tissue lymphoma misdiagnosed with tuberculosis: A case report.

Primary pulmonary mucosa-associated lymphoid tissue lymphoma (MALToma) is a rare subtype of non-Hodgkin lymphoma with a relatively low incidence rate clinically. Atypical clinical symptoms and nonspecific chest computed tomography features of the disease make it difficult to determine and treatment is delayed. We discuss the diagnosis and treatment of a patient with primary pulmonary MALToma to raise clinicians' awareness of this condition. A 66-year-old male patient with a medical history of tuberculosis has been experiencing progressive exacerbation of respiratory symptoms and nonresponsive treatment without an unclear diagnosis for 5 years. He was transferred to our hospital because a nonspecific soft tissue mass in the right upper lobe of the lung was found on his chest computed tomography. Laboratory results with serum immunofixation electrophoresis showed polyclonal immunoglobulin (Ig) G, IgM, IgA, and λ-light chain on admission. Pathological examination and immunohistochemical staining of lung biopsy revealed a definitive diagnosis of pulmonary MALToma with stage IV. The patient received immunotherapy with anti-CD20 monoclonal antibody (rituximab), and showed significant clinical improvement at the 6-month follow-up. Diagnosis of primary pulmonary MALToma mainly relies on histopathological examination, and comprehensive laboratory examinations are also necessary. Clinicians should combine laboratory tests (such as immunofixation electrophoresis in our case) to assist in medical diagnosis in cases of atypical clinical manifestations and imaging characteristics. Immunotherapy appears to be the main treatment protocol for advanced patients.

Elderly Female with Pulmonary Oedema Manifestation of Dengue Hemorrhagic Fever : a Case Report

Dengue Hemorrhagic Fever (DHF) is an arthropod borne viral disease. The main vector of the disease are the Aedes mosquitoes. Indonesia as one of the tropical nations in South Asia falls into one of the countries in which DHF is an endemic. The notable clinical symptoms are fever usually 400c with a biphasic pattern in 6% of DHF cases, body ache, muscles, retroorbital and joints, nausea, and vomiting. Fluid accumulation, due to plasma leakage, may occur in the abdominal cavities, pleural space, and even the lungs. The rise of non-communicable diseases like diabetes mellitus has impacted the clinical progression of DHF by increasing the risk of developing into dengue shock syndrome and atypical clinical manifestation of dengue plasma leakage and bleeding disorder. This case report discusses one of these atypical clinical manifestations of DHF. The case is an elderly female presenting in the emergency room with a DHF, Diabetes mellitus type 2, cardiomegaly, and during inpatient care developed a pulmonary Oedema. The patient experienced prolonged fever and on the 7th day of care develops a pulmonary oedema, the patient is then moved to the intensive care unit, and with proper treatment and monitoring was able to recover from the disease

A novel DLX3 mutation causes tricho-dento-osseous syndrome with abnormal enamel structure and formation

ObjectiveThis study aimed to identify a DLX3 gene mutation in a family with atypical clinical manifestations of tricho-dento-osseous syndrome (TDO) and its impact on tooth enamel thickness, microhardness, structure and formation. DesignWhole-exome sequencing detected DLX3 mutations in the family. Micro-CT, Vickers hardness tester, energy dispersive spectrometer and scanning electron microscopy were performed on the deciduous teeth of the proband and controls. In vitro experiments preliminarily verified the effect of this mutation on ameloblast differentiation and suggested possible molecular mechanisms. ResultsWe found a new DLX3 frame-shift mutation (NM_005220.3: c.604_605del: p. S202 *) in this family. Compared with control teeth, the mutant enamel showed a significant decrease in thickness, hardness and calcium content and an increase in magnesium content. The enamel structure appeared disordered. In an immortalized ameloblast-lineage cell (ALC) line, this mutation affected ameloblast differentiation and downregulated the expression levels of enamel matrix protein (EMP) genes (Amelx, Tuft1, Klk4, Ambn, Odam). A luciferase reporter assay demonstrated that this mutation significantly reduced the transactivation activity of DLX3 on Amelx/Odam/Klk4. ConclusionWe found a new DLX3 mutation in a Chinese family with enamel dysplasia and that this mutation may affect ameloblast differentiation by inhibiting the transcriptional activity of Amelx/Odam/Klk4, thereby interfering with enamel formation. Our findings further expand the variation spectrum and enrich the evidence of molecular genetics of DLX3 mutations.

Pharmacological activities and therapeutic potential of galangin, a promising natural flavone, in age-related diseases.

The extension of average life expectancy and the aggravation of population aging have become the inevitable trend of human development. In an aging society, various problems related to medical care for the elderly have become increasingly prominent. However, most of the age-related diseases have the characteristics of multiple diseases at the same time, prone to complications, and atypical clinical manifestations, which bring great difficulties to its treatment. Galangin (3,5,7-trihydroxyflavone) is a natural active compound extracted from the root of Alpinia officinarum Hance (Zingiberaceae). Recently, many studies have shown that galangin has potential advantages in the treatment of neurodegenerative diseases and cardiovascular and cerebrovascular diseases, which are common in the elderly. In addition, it also showed that galangin had prospective activities in the treatment of tumor, diabetes, liver injury, asthma and arthritis. This review aims to systematically summarize and discuss the effects and the underlying mechanism of galangin in the treatment of age-related diseases. We searched PubMed, SciFinder, Web of Science and CNKI literature database resources, combined with the keywords "galangin", "neurodegenerative disease", "tumor", "diabetes", "pharmacological activity", "drug combination", "pharmacokinetics", "drug delivery system" and "safety", and comprehensively reviewed the pharmacological activities and mechanism of galangin in treating age-related diseases. According to the previous studies on galangin, the anti-neurodegenerative activity, cardiovascular and cerebrovascular protective activity, anti-tumor activity, anti-diabetes activity, anti-arthritis activity, hepatoprotective activity and antiasthmatic activity of galangin were discussed, and the related mechanisms were classified and summarized in detail. In addition, the drug combination, pharmacokinetics, drug delivery system and safety of galangin were furtherly discussed. This review will provide reference for galangin in the treatment of age-related diseases. Meanwhile, further experimental research and long-term clinical trials are needed to determine the therapeutic safety and efficacy of galangin.

Case Report: Case report: An unusual presentation of granulomatosis with polyangiitis

Aim: We are reporting a case of an unusual presentation of granulomatosis with polyangiitis (GPA) with liver involvement. Case presentation: A 45-year-old male patient presented with erythematous plaques on the face and bilateral nasal obstruction. On physical examination, the patient had a ring-shaped squamous plaque on the face. The laboratory findings revealed an accelerated erythrocyte sedimentation rate at 100 mm/h, an elevated C-reactive protein at 66 mg/L, hyper gamma globulinemia 16 g/L and an elevated alkaline phosphatase (twice the upper normal limit). The craniofacial and thoracoabdominal computed tomography (CT) -scans showed ethmoid and maxillary sinusitis, low facial bone density, multiple mediastinal and hilar lymphadenopathy, diffuse small pulmonary nodules, and hepatomegaly. A cutaneous lesion biopsy, the nasal mucosa, and the liver showed a chronic inflammatory granulomatosis process with necrosis. Serum anti-neutrophil cytoplasmic antibody (ANCA) against PR3 was positive. The clinical, biological, radiological, and histological findings substantiated the diagnosis of GPA. The patient received systemic steroids combined with cyclophosphamide pulses on days 1, 14 and 28 and then he was lost to follow-up. Two-years later, he presented with a cardiac failure and skin ulcer in the right lower limb. A nasal endoscopic exam showed nasal septum cartilage perforation with resorption of the middle and inferior nasal concha. Two weeks later, he developed a diffuse alveolar hemorrhage and was therefore transferred to the intensive care unit but died of respiratory failure 3 days later. Conclusion: Clinicians should be aware of GPA atypical clinical manifestations.