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The nuclear receptor subfamily 5 group A member 1 (NR5A1) gene encodes NR5A1, also known as steroidogenic factor 1, a crucial transcriptional factor regulating adrenal and gonadal development and function. Although pathogenic variants in NR5A1 are known to cause a spectrum of disorders of sex development (DSD), individuals with 46,XY DSD with fully female internal and external genitalia are relatively rare. Herein, we present the case of a patient with 46,XY complete gonadal dysgenesis (CGD) who had a non-communicating rudimentary uterus due to a c.132_134del (p.Asn44del) heterozygous in-frame-deletion in NR5A1 that was diagnosed while treating a pelvic mass in which gynecological malignancy could not be disregarded. Unlike two previous cases with the p.Asn44del variant, this case presented with CGD, a severe DSD phenotype, and we found that the oligogenic inheritance of DSD-causative genes such as SRY, DHX37, SLC26A8, and CFTR may have affected the severity of the clinical phenotype.
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Patients with chronic kidney disease (CKD) sometimes experience gastrointestinal symptoms, such as nausea and vomiting. In addition, hypertension and CKD are closely linked, and sustained hypertension in children is associated with the progression of CKD, leading to early cardiomyopathy and premature atherosclerosis. These symptoms substantially affect the quality of daily life of CKD patients, and particularly in children with CKD, they may cause growth retardation. Therefore, establishing effective management methods to alleviate these symptoms is very important. Here, we report a case of a male patient who was born at 34 weeks of gestation weighing 1400 g. At birth, abdominal ultrasonography displayed left multicystic dysplastic kidney. From 6 months after birth, he was frequently hospitalized owing to refractory periodic vomiting. At 9 months old, he was diagnosed as having stage 3a CKD, and at 20 months old, he presented with stage 2 high blood pressure. In Japan, the uremic toxin adsorbent AST-120 and angiotensin-converting enzyme inhibitor-I (ACE-I) are not strongly recommended for CKD patients. However, after the patient underwent combination therapy of AST-120 and ACE-I, his frequent hospitalizations for refractory periodic vomiting ceased, and his blood pressure decreased. These results indicate that AST-120 and ACE-I are effective for refractory periodic vomiting and hypertension associated with CKD. The patient's height, weight, and mental development are catching up smoothly. The cause of the patient's refractory periodic vomiting remains unclear. However, his impaired kidney function owing to congenital anomalies of the kidney and urinary tract may have caused the refractory periodic vomiting and dehydration. The production of uremic toxins in CKD patients is thought to lead to the secretion of proinflammatory cytokines into the circulation. However, our patient had low serum levels of proinflammatory cytokines, and his serum levels of the chemokines CX3CL1 and CCL2 decreased with age, together with improvement in his clinical course. Therefore, some specific chemokines might be diagnostic and/or prognostic biomarkers of CKD.
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BACKGROUND: Pericytes play a role in the maintenance of the blood-brain barrier and neuroinflammation, attracting attention as to whether they are also involved in the pathogenesis of epilepsy.This study aimed to explore the relationship between West syndrome and pericytes. METHODS: Eighteen Japanese pediatric West syndrome patients and nine controls aged 2 years or younger were retrospectively enrolled in this study. We assessed theserumlevels of pericyte markers, serum PDGFRß (platelet-derived growth factor receptorß),CD13 (aminopeptidase N), and 27 cytokines in 17 pediatric patients with West syndrome and the control group. RESULTS: Patients with West syndrome exhibited significantly increased CD13 and decreased PDGFRß levels, compared with controls but not serum cytokine levels. These values did not differ significantly between symptomatic and idiopathic West syndrome. CONCLUSION: Pericytes might be implicated in the pathogenesis of West syndrome.
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Pericitos , Espasmos Infantiles , Niño , Humanos , Pericitos/metabolismo , Pericitos/patología , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Estudios Retrospectivos , Espasmos Infantiles/metabolismo , Antígenos CD13RESUMEN
The role of neuroinflammation in the pathophysiology of migraines is increasingly being recognized, and cytokines, which are important endogenous substances involved in immune and inflammatory responses, have also received attention. This review examines the current literature on neuroinflammation in the pathogenesis of migraine. Elevated TNF-α, IL-1ß, and IL-6 levels have been identified in non-invasive mouse models with cortical spreading depolarization (CSD). Various mouse models to induce migraine attack-like symptoms also demonstrated elevated inflammatory cytokines and findings suggesting differences between episodic and chronic migraines and between males and females. While studies on human blood during migraine attacks have reported no change in TNF-α levels and often inconsistent results for IL-1ß and IL-6 levels, serial analysis of cytokines in jugular venous blood during migraine attacks revealed consistently increased IL-1ß, IL-6, and TNF-α. In a study on the interictal period, researchers reported higher levels of TNF-α and IL-6 compared to controls and no change regarding IL-1ß levels. Saliva-based tests suggest that IL-1ß might be useful in discriminating against migraine. Patients with migraine may benefit from a cytokine perspective on the pathogenesis of migraine, as there have been several encouraging reports suggesting new therapeutic avenues.
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Citocinas , Trastornos Migrañosos , Masculino , Ratones , Femenino , Animales , Humanos , Factor de Necrosis Tumoral alfa , Interleucina-6 , Enfermedades Neuroinflamatorias , Trastornos Migrañosos/etiologíaRESUMEN
Pediatric mastocytosis is a relatively rare disorder and most commonly occurs as isolated cutaneous lesions. Although autism spectrum disorders have been reported to be associated with mastocytosis, no clear association between mastocytosis and motor and intellectual delay has been reported with the exception of the case that detected de novo monoallelic mutations in the GNB1 gene. Herein, we describe the case of a Japanese male pediatric patient aged two years and six months who had cutaneous mastocytosis accompanied by motor and intellectual delay without the presence of GNB1 mutation.
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Mannose-binding lectin (MBL) is crucial in first-line immune defenses. There are still many unknown factors regarding the mechanisms causing variability in the clinical course of coronavirus disease 2019 (COVID-19). In Japan, there have been few reports to date regarding the association between MBL and COVID-19. It has been demonstrated that the MBL2 gene B variant at codon 54 (rs1800450) is associated with variabilities in the clinical course of COVID-19. We aimed to investigate how the level of serum MBL and the codon 54 variant of MBL (rs1800450) affect the disease severity of COVID-19. A total of 59 patients from the fourth wave and 49 patients from the fifth wave in Japan were analyzed based on serum MBL levels using ELISA and the genotype of MBL2 codon 54 using PCR reaction. There was no significant association between serum MBL levels and age. MBL2 genotype was independent of age, there was no significant difference in different COVID-19 severities, MBL genotypes, and serum MBL levels. Binary logistic regression analysis to identify predisposing factors for severe COVID-19 symptoms demonstrated that patients with the BB genotype had a higher risk of death from COVID-19. Our results quantitatively demonstrated that the BB genotype might be a factor associated with death from COVID-19.
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Perinatal lethal Gaucher disease is a very rare variant of type 2 Gaucher disease that occurs in the neonatal period and leads to death in early infancy. The disease is characterized by hydrops fetalis or a collodion baby phenotype accompanied with progressive neurological manifestations, hepatosplenomegaly, thrombocytopenia, anemia, and failure to thrive. We report a case of perinatal lethal Gaucher disease treated with enzyme replacement therapy (ERT) who survived for 9 months and present a literature review of perinatal lethal Gaucher disease cases. The prognosis of perinatal lethal Gaucher disease is poor, and ERT is only effective in visceral manifestation. Therefore, palliative care should be recognized as a treatment option, and ERT employment needs to be discussed in this context.
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Enfermedad de Gaucher , Humanos , Femenino , Embarazo , Enfermedad de Gaucher/complicaciones , Glucosilceramidasa/genética , Terapia de Reemplazo Enzimático , Hidropesía FetalRESUMEN
Bacterial meningitis in infants is a life-threatening illness that survives significant neurological sequelae that remain in survivors. The current diagnostic gold standard for meningitis is bacterial isolation from culture or molecular diagnostics in the cerebrospinal fluid. The decision for antibiotics therapy before bacterial detection is made on microscopic and biochemical findings in the cerebrospinal fluid, however, some patient shows no microscopic finding and pleocytosis at the initial cerebrospinal fluid analysis. Herein, we report a case of late-onset group B Streptococcus serotype Ib meningitis that could be introduced with timelier antibiotic therapy even in the absence of pleocytosis without the detection of bacteria on smear at the initial CSF analysis.
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Edwardsiella tarda , a Gram-negative bacterium classified into the genus Enterobacteriaceae, causes self-limited gastroenteritis. Here, we report a case of E. tarda gastroenteritis in a previously healthy 12-year-old boy in whom inflammatory bowel disease was precluded by endoscopy and tissue biopsy due to 3-month history of diarrhea, abdominal pain and weight loss.
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Infecciones por Enterobacteriaceae , Gastroenteritis , Niño , Diarrea/complicaciones , Edwardsiella tarda , Enterobacteriaceae , Infecciones por Enterobacteriaceae/complicaciones , Infecciones por Enterobacteriaceae/diagnóstico , Infecciones por Enterobacteriaceae/microbiología , Gastroenteritis/microbiología , Humanos , MasculinoRESUMEN
INTRODUCTION: Improved routine immunizations in Japan have led to a reduction in vaccine-preventable diseases. Due to changes in the vaccination program, current young adults received their second vaccination for measles and rubella at different times depending on their birth year, and most of them have not been vaccinated against varicella and mumps. This study investigated the effect of vaccine programs on the immunity of people in Japan. METHODS: Immunoglobulin G antibody (IgG) titers against four viruses were determined by enzyme immunoassay in 795 students at a medical university. Titers for measles and rubella were compared according to the students' birth dates (Group 1: April 2, 1990-April 1, 2000; Group 2: April 2, 2000). RESULTS: The titers of students that satisfied the standard IgG values against measles, rubella, varicella, and mumps were 24.3%, 56.9%, 87.4%, and 47.2%, respectively. Measles and rubella titers were lower in group 2 (estimated mean period from last vaccination, 7.0 years) than group 1 (13.5 years) (p = 0.023 measles, p = 0.037 rubella), indicating attenuation of titers over time. Varicella and mumps antibody prevalence indicated that these infections were endemic, whereas rates of negative titers were higher than those for measles and rubella. CONCLUSIONS: IgG titers against viruses were affected by vaccination programs. Declining titers after vaccination should be monitored when the diseases are almost eliminated and boosting is absent. Antibody testing is meaningful for recommending vaccinations and for surveillance of waning immunity. Continuous improvements of vaccination program should be considered to prevent and eliminate diseases.
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Varicela , Sarampión , Paperas , Rubéola (Sarampión Alemán) , Anticuerpos Antivirales , Varicela/epidemiología , Varicela/prevención & control , Herpesvirus Humano 3 , Humanos , Inmunoglobulina G , Japón/epidemiología , Sarampión/prevención & control , Vacuna contra el Sarampión-Parotiditis-Rubéola/uso terapéutico , Paperas/tratamiento farmacológico , Paperas/prevención & control , Rubéola (Sarampión Alemán)/prevención & control , Vacunación , Adulto JovenRESUMEN
In Japan, the prevalence of low birth weight (LBW) has been estimated to be approximately 10%, which is the highest among developed countries. This high prevalence might affect the occurrence of LBW-associated diseases in the adult population of Japan. LBW has been recognized as a contributing factor to post-adaptive focal segmental glomerulosclerosis (FSGS) in adulthood; however, few reports to date have evaluated the clinical and pathological characteristics of post-adaptive FSGS. A 13-year-old girl was referred to our hospital owing to mild proteinuria, which was detected at a school urinary screening. She was born at a gestational age of 23 weeks, with a very LBW of 630 g. Dipstick urinalysis revealed grade (2+) proteinuria. Her serum creatinine level was 1.02 mg/dL, and she was diagnosed as having stage 2 chronic kidney disease (CKD). Her serum uric acid level was 7 mg/dL. Furthermore, her mother and 16-year old brother had hyperuricemia. A percutaneous renal biopsy leads to a diagnosis of FSGS. After 3 years of treatment with an angiotensin receptor blocker, her proteinuria decreased. However, her serum creatinine level was 1.07 mg/dL, and she still had stage 2 CKD. We considered that in this patient, the first hit was her LBW, and the second hit was hyperuricemia. The second hit might be associated with the development of CKD. The birth history of patients is not usually confirmed by nephrologists. Our case demonstrates that obtaining information regarding the preterm birth and LBW of patients is important in the diagnosis of noncommunicable diseases because school urinary screening is not routinely performed in countries other than Japan.
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Summary: We encountered a case of childhood-onset lymphocytic infundibuloneurohypophysitis, based on the MRI and endocrinological findings, with decreased function of the anterior and posterior lobes of the pituitary. Three years after the diagnosis, the patient developed non-alcoholic steatohepatitis (NASH), which was effectively treated by growth hormone (GH) supplementation. The present case demonstrated that NASH can be effectively treated by short-term GH supplementation, even in late childhood. Learning points: In recent years, the efficacy of growth hormone replacement therapy in normalizing the liver function of adult-onset growth hormone deficiency patients with non-alcoholic steatohepatitis (NASH) has been reported. Lymphocytic infundibuloneurohypophysitis is a very rare disease, particularly in childhood. We here presented a rare case of a child with lymphocytic infundibuloneurohypophysitis who developed NASH and showed substantial improvement in liver function after growth hormone treatment.
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Neuroinflammation has been implicated in the pathogenesis of West syndrome (WS). Inflammatory cytokines, including interleukin-1ß(IL-1ß), have been reported to be associated with epilepsy. However, the assessment of cytokine changes in humans is not always simple or deterministic. This study aimed to elucidate the immunological mechanism of WS. We examined the intracellular cytokine profiles of peripheral blood cells collected from 13 patients with WS, using flow cytometry, and measured their serum cytokine levels. These were compared with those of 10 age-matched controls. We found that the WS group had significantly higher percentages of inter IL-1ß, interleukin-1 receptor antagonist (IL-1RA)-positive monocytes, and interferon gamma (IFN-γ) in their CD8+ T cells than the control group. Interestingly, the group with sequelae revealed significantly lower levels of intracellular IFN-γ and IL-6 in their CD8+ T and CD4+ T cells, respectively, than the group without sequelae. There was no correlation between the ratios of positive cells and the serum levels of a particular cytokine in the WS patients. These cytokines in the peripheral immune cells might be involved in the neuroinflammation of WS, even in the absence of infectious or immune disease. Overall, an immunological approach using flow cytometry analysis might be useful for immunological studies of epilepsy.
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The roles of cytokines in the cerebrospinal fluid (CSF) of patients with acute encephalopathy remain unclear and controversial. In this study, the profiles of 26 cytokines and others were determined in 17 children with infection-associated neurological complications. Interleukin (IL)-12 levels were found to be high in a few of the patients. A comparison of the IL-12 levels in the CSF of patients demonstrated that IL-12 (p70) is almost always increased in those with encephalopathy. Levels of IL-12 in the CSF were highly correlated with the levels of PDGF-bb and IL-RA. IL-12 levels were found to be weakly correlated with IFN-γ levels, and strongly correlated with VEGF levels. These results demonstrate that IL-12 levels may affect the clinical symptoms of pediatric patients with encephalopathy.
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We investigated 22 cases of patients with myocarditis during respiratory syncytial virus (RSV) infection by a questionnaire survey, and performed a literature search to clarify their characteristics. The age distribution was divided into 2 groups, that is, 1 group comprised of patients younger than 4-years old and the other comprised patients older than 15 years. ECG demonstrated disturbance of the conduction system (AV block) in 7 out of 18 patients (38.8%), myocardial damage (ST-T change) in 9 out of 18 patients (50.0%), and tachycardia in 3 out of 18 patients (16.6%). Echocardiography displayed a robust decrease in left-heart function in 12 out of 14 patients. The outcome was 2 deaths, 1 pacemaker placement, 4 patients with mild sequel. Our data suggest that RSV myocarditis caused by RSV infection can be divided into 3 different pathophysiologies, characterized by disturbance of the conduction system, myocardial damage, and increase of autonomy.
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Riboflavin, a water-soluble member of the B-vitamin family, plays a vital role in producing energy in mitochondria and reducing inflammation and oxidative stress. Migraine pathogenesis includes neuroinflammation, oxidative stress, and mitochondrial dysfunction. Therefore, riboflavin is increasingly being recognized for its preventive effects on migraines. However, there is no concrete evidence supporting its use because the link between riboflavin and migraines and the underlying mechanisms remains obscure. This review explored the current experimental and clinical evidence of conditions involved in migraine pathogenesis and discussed the role of riboflavin in inhibiting these conditions. Experimental research has demonstrated elevated levels of various oxidative stress markers and pro-inflammatory cytokines in migraines, and riboflavin's role in reducing these marker levels. Furthermore, clinical research in migraineurs showed increased marker levels and observed riboflavin's effectiveness in reducing migraines. These findings suggest that inflammation and oxidative stress are associated with migraine pathogenesis, and riboflavin may have neuroprotective effects through its clinically useful anti-inflammatory and anti-oxidative stress properties. Riboflavin's safety and efficacy suggests its usefulness in migraine prophylaxis; however, insufficient evidence necessitates further study.