Background: Tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND) have unique, individual patterns that pose significant challenges for diagnosis, psycho-education, and intervention planning. A recent study suggested that it may be feasible to use TAND Checklist data and data-driven methods to generate natural TAND clusters. However, the study had a small sample size and data from only two countries. Here, we investigated the replicability of identifying natural TAND clusters from a larger and more diverse sample from the TOSCA study. Methods: As part of the TOSCA international TSC registry study, this embedded research project collected TAND Checklist data from individuals with TSC. Correlation coefficients were calculated for TAND variables to generate a correlation matrix. Hierarchical cluster and factor analysis methods were used for data reduction and identification of natural TAND clusters.

Severe combined immunodeficiencies (SCID) are a group of rare inherited disorders with profound defects in T cell and B cell immunity. From 2005 to 2010, our unit performed testing for IL2RG, JAK3, IL7R, RAG1, RAG2, DCLRE1C, LIG4, AK2, and ZAP70 mutations in 42 Chinese and Southeast Asian infants with SCID adopting a candidate gene approach, based on patient's gender, immune phenotype, and inheritance pattern. Mutations were identified in 26 patients, including IL2RG (n = 19), IL7R (n = 2), JAK3 (n = 2), RAG1 (n = 1), RAG2 (n = 1), and DCLRE1C (n = 1). Among 12 patients who underwent hematopoietic stem cell transplantation, eight patients survived. Complications and morbidities during transplant period were significant, especially disseminated bacillus Calmette-Guérin disease which was often difficult to control. This is the first cohort study on SCID in the Chinese and Southeast Asian population, based on a multi-centered collaborative research network. The foremost issue is service provision for early detection, diagnosis, management, and definitive treatment for patients with SCID. National management guidelines for SCID should be established, and research into an efficient platform for genetic diagnosis is needed.

BackgroundMany gynecological cancer survivors (GCS) have comorbid chronic diseases (CCD). This study was to estimate the impacts of CCD on quality of life (QOL) in GCS.MethodsWe collected cross-sectional self-reported survey data from 598 GCS between April and July 2013, in Shanghai, China. All the subjects were asked to complete a questionnaire containing the European Organization for Research and Treatment quality of life version 3 questionnaire (EORTC QLQ-C30) and questions on socio-demographic characteristics and CCD. In order to mitigate the bias caused by confounding factors, multiple linear models were employed to calculate adjusted means of QOL scores.ResultsApproximately three-quarters of subjects reported at least one CCD. The highest overall prevalence of all CCD was found in endometrial cancer survivors. Subjects with CCD generally reported lower scores for most EORTC QLQ-C30 scales when compared to subjects without CCD, indicating poorer QOL, particularly for cardiovascular diseases, respiratory diseases, digestive diseases, and musculoskeletal disease.ConclusionsThe CCD are common health problems among GCS. CCD have significantly negative influence on QOL, and GCS with CCD generally reported lower QOL scores. These findings suggested comprehensive cares for GCS.

Comorbidity with anxiety disorder is a relatively common occurrence in major depressive disorder. However, the unique and shared neuroanatomical characteristics of depression and anxiety disorders have not been fully identified. The aim of this study was to identify gray matter abnormalities and their clinical correlates in depressive patients with and without anxiety disorders.We applied voxel-based morphometry and region-of-interest analyses of gray matter volume (GMV) in normal controls (NC group, n = 28), depressive patients without anxiety disorder (DP group, n = 18), and depressive patients with anxiety disorder (DPA group, n = 20). The correlations between regional GMV and clinical data were analyzed.The DP group showed decreased GMV in the left insula (INS) and left triangular part of the inferior frontal gyrus when compared to the NC group. The DPA group showed greater GMV in the midbrain, medial prefrontal cortex, and primary motor/somatosensory cortex when compared to the NC group. Moreover, the DPA group showed greater GMV than the DP group in the frontal, INS, and temporal lobes. Most gray matter anomalies were significantly correlated with depression severity or anxiety symptoms. These correlations were categorized into 4 trend models, of which 3 trend models (ie, Models I, II, and IV) revealed the direction of the correlation between regional GMV and depression severity to be the opposite of that between regional GMV and anxiety symptoms. Importantly, the left INS showed a trend Model I, which might be critically important for distinguishing depressive patients with and without anxiety disorder.Our findings of gray matter abnormalities, their correlations with clinical data, and the trend models showing opposite direction may reflect disorder-specific symptom characteristics and help explain the neurobiological differences between depression and anxiety disorder.

Objective: This study was designed to compare the clinical manifestations, laboratory tests, etiology, and prognosis of children with acute rhabdomyolysis (RM) at various ages. This study was designed to analyze the risk factors for acute kidney injury (AKI) in children with RM and to identify the role of neuromuscular and autoimmune disease in children with RM. Methods: Clinical data for 55 children with RM were collected and statistically analyzed. Patients were stratified to an infant group (G1) (age <1 year), preschool group (G2) (age 1-6 year), school-age group (G3) (age 7-11 year), and an adolescent group (G4) (age 12-16 year). Results: The top three clinical manifestations were dark urine (52.7%), myalgia (38.2%), and fever (23.8%). Patients in G1 had fever (71.4%), vomiting (77.8%), and urinalysis abnormalities (14.3%), without triad clinical manifestations. Fifty percent of patients in G4 group had myalgia; 70.8% had dark urine; 75% had abnormal urine tests. The most common cause in each age group was as follows: sepsis (57.1%) in G1; hereditary neuromuscular diseases (44.4%) in G2; immune diseases (40%) in G3; strenuous exercise (50%) in G4. Logistic regression analysis shown that AKI was not corelated with age, gender, or peak creatine phosphokinase. AKI was, however, associated with presence of an electrolyte disorder. Conclusion: The clinical manifestations and laboratory findings in infants with acute RM are not typical and need to be taken seriously. The presence of an electrolyte disorder is a risk factor for AKI in children with RM. The most common pathogenesis of RM varies among age groups. Congenital hereditary metabolic disease and immune diseases should not be ignored as a cause of RM in children.

Background Tuberous sclerosis complex (TSC) is a rare multisystem autosomal dominant disorder caused by pathogenic variants in either the TSC1 or TSC2 gene. Common manifestations of TSC have been grouped into major and minor clinical diagnostic criteria and assessed in clinical routine workup. However, case studies point towards the existence of rare disease manifestations and to the potential association of TSC with malignant tumors. In this study we sought to characterize rare manifestations and malignancies using a large cohort of patients. Methods TuberOus SClerosis registry to increAse disease awareness (TOSCA) is a multicenter, international disease registry collecting clinical manifestations and characteristics of patients with TSC, both retrospectively and prospectively. We report rates and characteristics of rare manifestations and malignancies in patients with TSC who had enrolled in the TOSCA registry. We also examined these manifestations by age, sex, and genotype (TSC1 or TSC2). Results Overall, 2211 patients with TSC were enrolled in the study. Rare manifestations were reported in 382 (17.3%) study participants and malignancies in 65 (2.9%). Of these rare manifestations, the most frequent were bone sclerotic foci (39.5%), scoliosis (23%), thyroid adenoma (5.5%), adrenal angiomyolipoma (4.5%), hemihypertrophy and pancreatic neuroendocrine tumors (pNET; both 3.1%). These rare manifestations were more commonly observed in adults than children (66.2% vs. 22.7%), in females versus males (58.4% vs. 41.6%; except for scoliosis: 48.9% vs. 51.1%), and in those with TSC2 versus TSC1 (67.0% vs. 21.1%; except for thyroid adenoma: 42.9% vs. 57.1%). In the 65 individuals with reported malignancies, the most common were renal cell carcinoma (47.7%), followed by breast (10.8%) and thyroid cancer (9.2%). Although malignancies were more common in adult patients, 26.1% were reported in children and 63.1% in individuals < 40 years. TSC1 mutations were over-represented in individuals with malignancies compared to the overall TOSCA cohort (32.1% vs. 18.5%). Conclusion Rare manifestations were observed in a significant proportion of individuals with TSC. We recommend further examination of rare manifestations in TSC. Collectively, malignancies were infrequent findings in our cohort. However, compared to the general population, malignant tumors occurred earlier in age and some tumor types were more common.

Objective: Cytomegalovirus (CMV) encephalitis is a disease that primarily affects immunocompromised hosts. Only a few cases have been reported in immunocompetent individuals, especially in children. The aim of this study was to investigate the clinical characteristics of immunocompetent children with CMV encephalitis attending a single medical center in southwest China over a 15-year period. Methods: The medical records of children with confirmed CMV encephalitis who were hospitalized in the Children's Hospital of Chongqing Medical University during the years 2002-2017 were reviewed. An analysis of the clinical features, laboratory data, and the treatment response to antiviral therapy was performed. Results: The median age of the patients (n = 18) was 5.1 months. 'Seizures' was the earliest and most common neurological symptom, while fever and poor feeding were also present in most patients. Elevated cerebrospinal fluid (CSF) protein was the most noticeable biochemical finding. After treatment with twostage ganciclovir, all patients showed a steady clinical improvement. The total adverse drug reaction (ADR) rate was 27.3%, mainly presenting as effects on the hematopoietic system and liver. During follow-up ranging from 3 to 36 months, nine patients showed a complete recovery. At the stage of diagnosis, CMV PCR of CSF was positive in all patients, while anti-CMV IgM was positive in 77.8% of patients. After treatment with two-stage ganciclovir, all patients showed a negative result for CMV genome in the CSF and a clear decrease in the urine. Conclusions: The possibility of CMV encephalitis in the immunocompetent child should be kept in mind, especially in those younger than 6 months of age. Suspicion for a diagnosis of CMV encephalitis is needed in the presence of unexplained prominent seizure, fever, poor feeding, and a marked elevation of protein level in the CSF. CMV PCR assays of CSF are necessary to determine the etiology. Furthermore, measurement of the CMV load in CSF and urine may be useful for evaluating the response to treatment and the outcome. Ganciclovir may lead to clinical improvement with limited ADR. CMV encephalitis in the immunocompetent infant does not necessarily indicate a poor short-term prognosis.

Rationale:Autoimmune encephalitis related to many antibodies against neuronal cell surface or synaptic proteins, it is increasingly recognized as the cause of a variety of neuropsychiatric syndromes.Patient concerns:The two pediatric cases were about autoimmune encephalitis with rare complication. One patient was a 11-year-old girl and was diagnosed with Voltage-Gated Potassium Channel complex (VGKC) antibody-mediated encephalitis with rhabdomyolysis; the other was also a 11-year-old girl and was diagnosed with anti- N-methyl-D-aspartate receptor (NMDAR) encephalitis.Diagnoses:Both patients were diagnosed as autoimmune encephalitis with rare complication.Interventions:Intravenous methylprednisolone, oral prednisone and intravenous immunoglobulin was administered to both patients.Outcomes:One patient was discharged after a half month's hospitalization; the other was finally with intestinal function failure, gradually developed multiple organ failure, and eventually died.Lessons:The pathogenic mechanism of autoimmune encephalitis associated with autoimmune disease is not fully understood, but may be related to a common immune pathological mechanism with variance in susceptibility caused by genetic or environmental factors.