Atypical Clinical Manifestations Research Articles

Fatal systemic herpes simplex virus infection with atypical clinical manifestation early after living donor liver transplantation

Fatal systemic herpes simplex virus infection with atypical clinical manifestation early after living donor liver transplantation

Spinocerebellar Ataxia Type 10 with Atypical Clinical Manifestation in Han Chinese.

Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant cerebellar ataxia accompanied by extracerebellar signs and other neurological disorders. It is caused by an expansion of the ATTCT pentanucleotide repeat in intron 9 of ATXN10. Cases of SCA10, formerly confined to America, have been reported in Europe and Asia. In the present study, we aim to report an atypical SCA10 family in China and provide a reference for the diagnosis of SCA10 in Asia by comparing their clinical and genetic features with former SCA10 pedigrees. Genomic DNA was extracted from patients and subjected to RP-PCR (repeat-primed PCR), Southern blotting, and haplotype analysis to determine the genetic pathogenesis. Patients with SCA10 in this pedigree demonstrated atypical SCA10 manifestations, including the absence of seizures and ocular abnormalities. Magnetic resonance imaging (MRI) showed cerebellar atrophy in five patients with available data. RP-PCR and Southern blotting revealed abnormal expansion. Analysis of single nucleotide polymorphisms (SNPs) surrounding the SCA10 locus in the proband and other affected family members revealed the "C-expansion-G-G-C" haplotype, consistent with former studies. These findings imply that the SCA10 mutation may have occurred before the Amerindian migration from East Asia to North America. It also suggested that SCA10 should be taken into account during differential diagnosis in patients of Asian ancestry, even if they do not present with typical features such as epilepsy.

Gene analysis and clinical features of 22 GNE myopathy patients.

GNE myopathy is an autosomal recessive distal myopathy caused by a biallelic mutation in UDP-N-acetylglucosamine 2-epomerase/N-acetylmannosamine kinase. In this study, we discuss the clinical features, pathological characteristics, genetic profiles, and atypical clinical manifestations of 22 Chinese GNE patients. Retrospective analysis was performed for GNE myopathy patients at our institute between 2005 and 2021. Histopathological analysis and gene testing were done according to standard protocols. Molecular analysis revealed 14-reported and 7 novel mutations, including c.125G > A (p.P42Q), c.226G > A (p.V76I), c.970C > G (p.H324D), c.155A > G (p.D52G), c.1055G > A (p.R352H), c.1064G > A (p.G355E), and c.491T > C (p.I164T) in GNE. D207V was the most frequent mutation showing an allele frequency of 25%. A total of 21 patients presented classic clinical manifestation, and only 1 patient had signs of proximal muscle weakness. A patient containing p.V603L and p.R160X mutations showed idiopathic thrombocytopenia and distal weakness. There were 4 female patients who experienced rapid deterioration after pregnancy. Our study revealed 7 novel mutations in GNE, where p.D207V was shown as a potential hotspot mutation in Chinese patients. Idiopathic thrombocytopenia should be a concern in GNE myopathy patients. Twenty-seven percent of female patients experienced rapid deterioration during pregnancy or after delivery.

Evaluation of Molecular Test for the Discrimination of "Naked" DNA from Infectious Parvovirus B19 Particles in Serum and Bone Marrow Samples.

Low levels of parvovirus B19 (B19V) DNA can be detected in the circulation and in different tissue of immunocompetent individuals for months or years, which has been linked to inflammatory diseases such as cardiomyopathy, rheumatoid arthritis, hepatitis, and vasculitis. However, the detection of B19V DNA does not necessarily imply that infectious virions are present. This study aimed to evaluate the method based on the Benzonase® treatment for differentiation between the infectious virions from “naked” DNA in serum and bone marrow (BM) samples to be useful for the B19V routine diagnosis. In addition, we estimated the period of viremia and DNAemia in the sera and bone marrow of nonhuman primates experimentally infected with B19V. Serum samples from ten patients and from four cynomolgus monkeys experimentally infected with B19V followed up for 60 days were used. Most of the human serum samples became negative after pretreatment; however, only decreased viral DNA loads were observed in four patients, indicating that these samples still contained the infectious virus. Reduced B19V DNA levels were observed in animals since 7th dpi. At approximately 45th dpi, B19V DNA levels were below 105 IU/mL after Benzonase® pretreatment, which was not a consequence of active B19V replication. The test based on Benzonase® pretreatment enabled the discrimination of “naked DNA” from B19V DNA encapsidated in virions. Therefore, this test can be used to clarify the role of B19V as an etiological agent associated with atypical clinical manifestations.

Invasive Aspergillus outbreak in inhalation injury: a case presentation and literature review

BackgroundInvasive pulmonary aspergillosis often occurs in patients with poor immune function, who abuse steroids or broad-spectrum antibiotics, or who use intravenous drugs. Among the Aspergillus genus of pulmonary infection, Aspergillus fumigatus is the most important pathogen, followed by Aspergillus flavus, Aspergillus niger, and Aspergillus terreus. Inhalation injury complicated by Aspergillus infection has atypical clinical manifestations. Diagnosis is difficult, and it is easy to make mistakes in treatment. Moreover, there are few cases of burn inhalation injury complicated with pulmonary Aspergillus.Case presentationWe report a case of severe burns combined with severe inhalation injury, early pulmonary aspergillosis, and severe respiratory failure due to treatment discontinuation. Through analyzing the processes of diagnosis and treatment in the present case and performing a literature review, we explore feasible diagnosis and treatment plans.ConclusionsEarly application of a variety of diagnostic measures can be used to identify Aspergillus infection, and targeted anti-infection treatment is likely to reverse a severe adverse prognosis.

Genetic analysis of a Chinese pedigree affected with Becker muscular dystrophy with myalgia as the main feature

To explore the genetic basis of a Chinese pedigree affected with Becker muscular dystrophy (BMD) with myalgia as the main feature. Clinical data of the patients and results of auxiliary examinations were retrospectively analyzed. Multiplex ligation-dependent probe amplification and high-throughput sequencing were used to detect potential variants. Sanger sequencing was used to verify the results. The clinical manifestations of the proband included myalgia and elevated serum creatine kinase, which is similar to another patient from the pedigree. Genetic testing revealed that the two patients both harbored hemizygous deletions of exons 10 to 29 of the DMD gene, for which the mother was a carrier. The same deletion was not found in his father. Based on the guidelines from American College of Medical Genetics and Genomics, the deletion was predicted to be pathogenic (PVS1+PM2+PP1). Myalgia with elevated serum CK may be atypical clinical manifestations of BMD and may be associated with variants in the rod domain of the DMD gene. The deletion of exons 10 to 29 of the DMD gene probably underlay the BMD in this pedigree.

Kawasaki Disease with Peripheral and Facial Gangrene: A Case report and review of literature

With the onset of the SARS-CoV-2 pandemic, Kawasaki Disease (KD) has come to the fore with its many atypical manifestations. Atypical clinical neurological, ophthalmological, musculoskeletal, gastrointestinal and pulmonary manifestations in a febrile child with raised markers should prompt the clinician to think of Kawasaki disease. Peripheral gangrene is a rare atypical manifestation of KD reported in infancy. We present a three-and-a-half-year-old boy with extensive gangrene all four limbs and face along with purpura fulminans. He was successfully treated with two doses of intravenous immunoglobulin (IVIG) and infliximab, with no residual gangrene. This case highlights that very severe forms of Kawasaki disease require IVIG, pulse steroids as well as infliximab for adequate control and complete resolution of the disease.

A Retrospective Study of 105 Patients with Elastolytic Giant Cell Granuloma and a Proposal for a New Clinical Classification.

Elastolytic giant cell granuloma, an idiopathic granulomatous dermatosis, is characterized by annular plaques on sun-exposed areas, and has been termed actinic granuloma or annular elastolytic giant cell granuloma. Many atypical clinical manifestations and lesions involving sun-protected areas have been reported. The aims of this retrospective study of 105 patients were to summarize the clinical and histological features of patients with this condition; to provide evidence for the viewpoint that elastolytic giant cell granuloma is a better term to include all clinical morphological types presenting with elastolysis, elastophagocytosis, and an infiltrate of multinucleated giant cells histologically; and to establish a new clinical classification. The varying clinical manifestations were further categorized into annular, papular, giant, mixed and generalized forms. The pathological manifestations were classified into giant cell, necrobiotic, histiocytic, sarcoidal and mixed patterns. Diabetes mellitus or impaired glucose tolerance were the most commonly identified comorbidities. Oral low-dose corticosteroid may be an effective treatment.

Could distal variants in ALG13 lead to atypical clinical presentation?

Congenital disorders of glycosylation (CDG) represent a wide range of some 150 inherited metabolic diseases, continually expanding in terms of newly identified genes and the heterogeneity of clinical and molecular presentations within each subtype. Heterozygous pathogenic variants in ALG13 are associated with early-onset epileptic encephalopathy, typically in females. The majority of subjects described so far harbour one of the two recurrent pathogenic variants, namely p.(Asn107Ser) and p.(Ala81Thr) in the C-terminal glycosyltransferase domain. We report a novel ALG13 variant (c.1709G > A, p.(Gly570Glu)) in an adult female with unremarkable past developmental and medical history, except for mild kinetic tremor. Our proband presented with acute onset of neurological and psychiatric features, along with liver dysfunction, during pregnancy, all of which gradually resolved after delivery. The proband's newborn baby died at 22 days of life from neonatal liver disease, due to gestational alloimmune liver disease (GALD). Functional assessment on fibroblasts derived from our case showed alterations in 2 of 3 cellular glycosylation markers (LAMP2, Factor IX), suggesting a functional effect of this novel ALG13 variant on glycosylation. This paper raises the possibility that variants outside the glycosyltransferase domain may have a hypomorphic effect leading to atypical clinical manifestations.

Giant dorsal lipofibromatosis in an infant: a case report

BackgroundLipofibromatosis is a rare, benign, soft tissue tumor that usually presents in children. Low incidence and lack of specificity in clinical presentation make its diagnosis difficult.Case presentationThis is a case report of a patient with a giant lipofibromatosis on the back that resembles an infantile hemangioma, which posed great difficulty in diagnosis due to atypical clinical manifestations. After the postoperative pathological and immunohistochemical examination and fluorescence in situ hybridization, the patient was finally diagnosed with lipofibromatosis.ConclusionsThe incidence of fibromatosis was low. This case presents an atypical clinical manifestation since the tumor growth was on the back, and this can easily cause misdiagnosis. This case suggests that the diagnosis of lipofibromatosis depends on the pathology and fluorescence in situ hybridization.

Clinical Analysis of 50 Cases of Primary Pulmonary Lymphoma: A Retrospective Study and Literature Review.

Objective: This study aimed at to raise the awareness understanding of primary pulmonary lymphoma (PPL) by analyzing the clinical manifestation, imaging, pathology, diagnosis, treatment, and prognostic features of 50 cases of PPL. Methods: The study of 50 individuals with PPL diagnosed at the First affiliated hospital of Nanchang university between January 2009 and December 2019 was performed. Results: Overall, 27 males and 23 females were enrolled, with an average age of 57.6 ± 15.6 years. The primary symptoms included, cough (n = 37), expectoration (n = 25), sputum with blood (n = 12), and chest pain (n = 12). Two individuals had Hodgkin's lymphoma and 48 patients had non-Hodgkin's lymphoma (NHL). We divided the NHL cases into mucosa-associated lymphoid tissue lymphoma (MALT) (n = 21), diffuse large B-cell lymphoma (n = 12), small lymphocytic lymphoma (n = 2), mantle B-cell lymphoma (n = 2), follicular lymphoma (n = 1), B-cell lymphoma without further classification (n = 8), and T-cell lymphoma (n = 2). The imaging findings revealed that unilateral lung involvement was more common among the patients. The longest follow-up duration up to December 2019 was 123 months with 40 surviving patients. The 5-year overall survival and progression-free survival were 46.7% and 44.4%, respectively. Age was an independent predictive factor for the 5-year survival (hazard ratio, 8.900; P = .038), (P < .05). Conclusion: PPL is a uncommon disease with atypical clinical manifestations and is often misdiagnosed. Immunohistochemistry is currently the standard used in pathologic evaluation of PPL. MALT prognosis is better in contrast with other kinds of PPL. Surgery or radiotherapy can be considered in patients with limited lesions, and chemotherapy is the first treatment option for diffuse lesions. Age of ≥ 60 years was reported as an independent adverse predictive factor.

Features of the course of covid -19 in children of southern ukraine (experience of the winter season 2021-2022)

Introduction. The infection caused by the SARS-CoV-2 virus can have different clinical manifestations, affect both the respiratory system and other organ systems, and the course can vary from asymptomatic or mild to severe, requiring hospitalization. The diversity of clinical manifestations of the disease, the peculiarities of the course of the disease in different age periods force doctors to be attentive to any symptoms in patients, both those related to the respiratory system and atypical complaints. Any new information about the peculiarities of the course of the coronavirus infection, age differences, "masks" of the disease, typical and atypical clinical manifestations is important. Purpose of research. The purpose of the study was to study and analyze the clinical features of the course of the disease COVID-19 in children in the winter season of 2021-22. Materials and methods. Retrospective analysis of the disease histories of children with a severe course of COVID-19 was carried out. Results. School-age children predominated among those hospitalized, which emphasizes the epidemiological significance of this particular age category in implementation of timely quarantine measures in educational institutions. Among the clinical manifestations, both typical signs of damage to the respiratory system and symptoms of damage from the gastrointestinal tract were registered. A characteristic feature of the course of COVID-19 in the specified winter season of 2021-22. a mixed infection with rotavirus and influenza was registered, which was not observed during the previous wave of the disease. Conclusions. The identified features of the course of COVID-19 in children will help to improve algorithms for providing assistance topatients of different age categories and predict the course of the disease.

Clinical Characteristics of Chlamydia psittaci Pneumonia Confirmed by Metagenomic Next-Generation Sequencing

Chlamydia psittaci pneumonia has atypical clinical manifestations and the diagnosis may be missed by traditional methods of microbiological diagnosis. Twelve cases of Chlamydia psittaci pneumonia diagnosed by metagenomic next-generation sequencing (mNGS) in Huizhou Central People's Hospital in China between January 2020 and August 2021 were reviewed and analyzed, retrospectively, using hospital records, the clinical characteristics, treatment, and prognosis. Ten of the 12 cases (83%) were associated with a definite history of bird/poultry contact. Common symptoms included high fever, cough, fatigue, anorexia (12/12, 100%), dyspnea (11/12, 92%), and changes in the level of consciousness and headache (5/12, 42%). There was a marked increase in C-reactive protein and D-dimer levels, but white blood cells and neutrophils were normal or slightly increased. Nine patients (75%) had liver enzyme abnormalities, and six (50%) had cardiac insufficiency and myocardial injury. There was no correlation between the mNGS sequence number of Chlamydia psittaci and the pneumonia severity. The chest imaging manifestations were mainly large areas of consolidation, predominantly in the lower lung lobes. Monotherapies or combinations of doxycycline, moxifloxacin/levofloxacin, and azithromycin were effective for treating Chlamydia psittaci pneumonia. The use of mNGS increases the probability of diagnosing Chlamydia psittaci pneumonia, and good prognosis can be achieved with timely use of appropriate antibiotics.

Inaugural Seizures Revealing COVID-19 in an Immunocompetent Infant at the University Teaching Hospital (UTH) of Bouak&amp;#233;

Introduction: Children are likely to present with atypical and non-specific clinical manifestations of COVID-19, unlike adults. The aim of this observation is to identify the difficulties related to the diagnosis and the curative and preventive management of SARS-CoV-2 infection in children. Observation: This is a 15-month-old infant admitted for febrile seizures. The interrogation revealed signs evolving 48 hours before his admission marked by post-prandial vomiting, wet cough, hypotonia, food refusal, incessant crying, fever, and seizures. His antecedents can be summed up as an uneventful pre- and per-natal period, good eating habits, good psychomotor and staturo-ponderal development, and outdated vaccination. The physical and paraclinical examination made it possible to retain the diagnosis of severe pneumonia. The initial management consisted of oxygenation, hydroelectrolyte intake, antibiotic therapy, and neurosedation. The evolution 3 days later was marked by a worsening of the clinical features, and the hypothesis of infection with SARS-CoV-2 was raised. The nasopharyngeal swab for COVID-19 RT-PCR performed was positive. The infant was isolated in the intensive care unit, where he received oxygen therapy with a mask, enteral nutrition, antibiotic therapy, corticosteroid therapy, and adequate nursing. The evolution was favorable 48 hours later. In addition, his asymptomatic mother and 14-year-old brother were placed in isolation after a positive RT-PCR COVID-19 test. Her father who was very often away from home for professional reasons was negative for COVID-19 RT-PCR. They all four live in the same 3-room house. Conclusion: Childhood COVID-19 has many facets. Clinicians should think about it in the face of any infectious manifestation, in order to avoid delays in treatment and improve the prognosis.

Analysis of imaging characteristics of blunt traumatic aortic dissection: an 8-year experience.

Traumatic aortic dissection (TAD) has a low incidence but extremely high mortality. It always presents atypical clinical manifestations that are easily missed or misdiagnosed. This study mainly aims to describe the imaging characteristics and management of TAD patients. A retrospective analysis of 27 blunt TAD patients was performed between 2013 and 2020. Demographic features, imaging characteristics, and management were analyzed. Twenty-seven patients with type B aortic dissection (age 56.04±16.07 years, 20 men) were included. Aortic intimal tears were mostly initiated from the aortic isthmus. The sizes of the proximal intimal tears in the greater curvature were larger than those in the lesser curvature (1.78±0.56 cm vs. 1.24±0.52 cm, P=0.031). Compared with those in the control group, the maximum diameters of the aortic arch, thoracic aorta, and abdominal aorta in the TAD patients were all significantly widened (all P<0.050). Multivariate logistic regression analysis showed that the maximum diameter of the thoracic aorta was an independent risk factor for TAD, with a predictive value with an area under the receiver operating characteristic curve (AUC) of 0.673. Finally, 26 patients successfully underwent delayed thoracic endovascular aortic repair (TEVAR), and the remaining one patient was treated conservatively. No progression of aortic dissection or death occurred during the six-month follow-up period. In blunt trauma, the aortic isthmus is the most common site of proximal intimal tears. An accurate diagnosis of TAD requires an overall consideration of medical history and imaging characteristics. Delayed TEVAR might be an effective therapeutic option for TAD.

Chapter 25 - The temporal lobe in typical and atypical Alzheimer disease

Alzheimer disease (AD) is defined neuropathologically by abnormal extra-cellular β-amyloid plaques combined with intraneuronal tau aggregation. Patients sharing the same neuropathological features but presenting different clinical manifestations and evolutions have led to the notion of AD spectrum. This spectrum encompasses typical and atypical forms of AD. For all of them, specific parts of the temporal lobes, as well as their structural and functional connections with other brain regions, are affected. In typical amnestic late-onset Alzheimer's disease (>65 years old; LOAD), tau pathology gradually spreads to the brain from the medial temporal lobe (MTL). MTL is an inhomogeneous structure consisting of several subregions densely connected to each other and to other cortical and subcortical brain regions. These regions play a crucial role in the storage of information in episodic memory. In less common early-onset AD (<65 years old; EOAD), a large proportion of patients presents atypical clinical manifestations, in which memory impairment is not inaugural and predominant. Instead, these patients have predominant and/or isolated deficits in language, visuospatial, motor, or executive/behavioral functions. In atypical variants, brain damage is mainly centered on the posterior regions, with relative sparing of the MTL. However, the temporal lobe also appears to be variably and specifically damaged in some subtypes of EOAD. For example, the left superior temporal gyrus is the core of brain damage in the language variant, as well as the ventral regions of the temporal lobe play an important role in the clinic of the visual variant.

Experience Professional dermatomycosis of the face, neck and upper part of chest caused by T. mentagrophytes

A 43-year-old female zoologist has an occupational dermatomycosis of the face, neck and upper part of chest caused by T. mentagrophytes. It was mistakenly diagnosed and treated as "Rosacea, papulopustular subtype, ocular rosacea" for 1.5 years. Symmetrical, atypical clinical manifestations with recurrent blepharoconjunctivitis developed as a result of self-treatment using a topical steroid. The detection of cicatrizing folliculitis in the eyebrow area and an arcual peripheral edge in fresh foci on the chest helped to suspect dermatomycosis. The definitive diagnosis was made after the detection of abundant coarse septate mycelium during microscopic investigation of skin scales from foci on the face and chest with 30% KOH and an abundant growth of Trichophyton mentagrophytes during a cultural research study of skin scales, eyebrow hair and eyelashes from lesions. The use of terbinafine for 4 weeks led to the recovery of the patient.

MNGS helped diagnose scrub typhus presenting as a urinary tract infection with high D-dimer levels: a case report

BackgroundScrub typhus is caused by O. tsutsugamushi and spreads through mite larvae biting the skin. Classic symptoms of the disease are eschar and lymphadenopathy. Previous reports have revealed clinical manifestations of scrub typhus, including gastrointestinal symptoms, meningoencephalitis, ocular flutter, pneumonitis, acute respiratory distress syndrome, and acute kidney injury. However, cases of scrub typhus presenting as a urinary tract infection (UTI) with high D-dimer levels could be easily misdiagnosed when clinical attention is insufficient, resulting in difficulty in making a timely diagnosis of the infection. Metagenomics next-generation sequencing (mNGS) is a revolutionary and highly sensitive method that may help in diagnosing atypical cases, even when trace amounts of pathogens are present.Case presentationA 52-year-old female presented with a 10-day history of fever, chills, headache and myalgia. She was initially diagnosed with influenza at a local clinic. Various antibacterials were used on the 2nd–12th day onwards; however, her symptoms persisted and were followed by increased urination duration, frequency, urgency and dysuria for 2 days. Orientia tsutsugamushi was confirmed as the pathogen responsible for the infection through mNGS analysis of her blood samples from Day 13 onwards. The patient’s temperature changed remarkably 24 h after the initiation of doxycycline. Over the next 48 h (i.e., Day 15 onwards), the patient showed clinical improvement. She recovered and was discharged from the hospital.ConclusionsScrub typhus can present atypical clinical symptoms, such as UTIs, in a febrile patient. mNGS may be a useful method for identifying O. tsutsugamushi infection in patients with atypical clinical manifestations.

Fatal systemic herpes simplex virus infection with atypical clinical manifestation early after living donor liver transplantation

Fatal systemic herpes simplex virus infection with atypical clinical manifestation early after living donor liver transplantation

Abstract 13685: Combined Genetic Defects of Sitosterolemia and Familial Hypercholesterolemia

Background: Familial hypercholesterolemia (FH) is an inherited disorder caused by mutations in the genes in the LDL receptor pathway, including LDLR , PCSK9 , APOB, and ARH . Defective uptake of LDL by the liver increases plasma LDL-cholesterol (LDL-C) levels, leading to an increased risk of coronary heart disease. The differential diagnosis of FH includes sitosterolemia which is a rare autosomal recessive disorder caused by mutations in ABCG5 or ABCG8 . Case presentation: Here we present a rare case of sitosterolemia with a genetic diagnosis of FH. A 64-years-old woman, clinically diagnosed as FH with Achilles tendon thickness (&gt;18 mm on X-ray imaging), had been taking statins only intermittently due to muscle pains. The combinatorial therapy with ezetimibe decreased her plasma LDL-C levels to around 90-250 mg/dL with variable adherence to statins and dietary management. Further addition of a PCSK9 inhibitor (evolocumab) was largely ineffective with plasma LDL-C levels of 90-190 mg/dL. A systemic medical evaluation revealed persistent joint pains of unknown etiology and slightly decreased platelet count. These clinical features led us to suspect sitosterolemia. Biochemical and genetic analyses: Plasma concentration of sitosterol was elevated (16.8 mg/dL). Genetic testing was performed after obtaining informed consent. All procedures were subjected to approval by the human genome, gene analysis research ethics committee of the University of Tokyo. In addition to a heterozygous missense mutation in LDLR (p.Arg115His), a homozygous nonsense mutation in ABCG5 (p.Tyr188Ter) was identified. No rare variants were found in PCSK9 nor ABCG8 . Conclusions: To our knowledge, this is the first case of a combined genetic defect of sitosterolemia and FH. Atypical clinical manifestations such as large fluctuations of LDL-C levels, unresponsiveness to a PCSK9 inhibitor, arthralgia, and a reduced platelet count led to the genetic diagnosis. Our case is informative in the perspective of precision medicine, highlighting the importance of systemic medical evaluation to select patients who will be benefited more from genetic testing as well as the necessity of future drug development for this rare and intractable disease.