Pediatric endocrinopathies related to COVID-19: an update.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the seventh coronavirus to be linked to human disease. The SARS-CoV-2 virus may have several pathophysiologic interactions with endocrine systems, resulting in disruptions in glucose metabolism, hypothalamus and pituitary function, adrenal function, and mineral metabolism. An increasing amount of evidence demonstrates both the influence of underlying endocrine abnormalities on the outcome of COVID-19 and the effect of the SARS-CoV-2 virus on endocrine systems. However, a systematic examination of the link to pediatric endocrine diseases has been missing. DATA SOURCES: The purpose of this review is to discuss the impact of SARS-CoV-2 infection on endocrine systems and to summarize the available knowledge on COVID-19 consequences in children with underlying endocrine abnormalities. For this purpose, a literature search was conducted in EMBASE, and data that were discussed about the effects of COVID-19 on endocrine systems were used in the current study. RESULTS: Treatment suggestions were provided for endocrinopathies associated with SARS-CoV-2 infection. CONCLUSIONS: With the global outbreak of COVID-19, it is critical for pediatric endocrinologists to understand how SARS-CoV-2 interacts with the endocrine system and the therapeutic concerns for children with underlying problems who develop COVID-19. While children and adults share certain risk factors for SARS-CoV-2 infection sequelae, it is becoming obvious that pediatric responses are different and that adult study results cannot be generalized. While pediatric research gives some insight, it also shows the need for more study in this area.

Familial Hemophagocytic Lymphohistiocytosis secondary to UNC13D mutation: a report of two cases.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease characterized by some clinical signs (e.g., non-remitting fever, hepatosplenomegaly) and laboratory findings (e.g., cytopenia, increased ferritin level, hypofibrinogenemia, lipid disorders, coagulopathy, and multiple organ failure). Depending on the etiology, HLH is divided into familial (i.e., primary) and acquired (i.e., secondary) forms. Familial HLH (FHL), an autosomal recessive condition, is classified into five subtypes based on underlying genetic defects. The PRF1, STX11, UNC13D, HPLH1, and STXBP2 are the most well-known genes of this type which are related to granule-mediated cytotoxic T and Natural killer (NK) cells. The treatment is based on the HLH-2004 protocol. CASE PRESENTATION: The current report presents two cases of HLH with presentations different from each other and previously reported cases. Case 1 was a 15-month-old boy with fever, skin rash, splenomegaly, and bicytopenia, raised triglyceride levels, AST (aspartate transaminase), and ALT (alanine aminotransferase), normal ferritin, and abundant hemophagocytic cell in bone marrow aspiration. He was diagnosed with HLH and received HLH protocol as treatment. The patient had a homozygous intronic mutation; NM_199242: c.2448-13G > A in UNC13D. The associated disease was Familial Hemophagocytic Lymphohistiocytosis 3 (FHL3). Case 2, a 37-day-old female presented with fever, a history of neonatal cholestasis, and huge hepatosplenomegaly. Her whole-exome sequencing report manifested that the patient had the same mutation as case 1. Unfortunately, both patients passed away. CONCLUSION: The sequencing of the entire UNC13D gene (coding and non-coding regions) is an applicable and valuable diagnostic procedure for the detection of deep intronic splicing variants and large inversions in patients with atypical manifestations of HLH (such as normal ferritin or triglyceride and cholesterol).

Relationship between a near Melanocortin-4 receptor gene variant and puberty timing in children is vague unlike obesity.

Background: Obesity is a complicated phenomenon which is a combination of genetic, environmental, and psychological factors. Genetic factors of obesity play an important role in individual risk. It is well known that obese children have disturbed puberty timing. To the best of our knowledge, no study has been performed to investigate the association between MC4R gene mutation and puberty timing. Methods: This study was performed as a cross-sectional study evaluating the near MC4R rs17782313 variation in 60 obese children and 98 healthy non obese children. Weight, height, BMI ( Body Mass Index ), BMI z-score (BMIz), family history of diabetes mellitus and obesity, the age of the obesity onset, overeating behavior, type of obesity (central or general) and puberty stage were evaluated in 60 obese children. Results: The average age of the participants was 14.87 (+/- 1.3) years, with average weight and BMI of 90.77 (+/-12.2) Kg and 31.72 (+/-4.35) Kg/m2, respectively. Compared to healthy non obese patients, those with C-T genotype (C-T Vs. T-T and C-C) had higher odds of obesity than those with T-T and C-C genotype (p < 0.0001) while genotype TT showed significant protective effect (p = 0.0007). The heterozygote individuals (CT) have a higher BMIz than homozygote ones (CC and TT) (2.8 vs. 2.5 Kg/m2, p = 0.04). Conclusions: children with CT genotype have 5.1 increased risk of obesity. While genotype TT showed significant obesity protective effect. We did not find association of this polymorphism with either childhood eating disorders or puberty. It is recommended to perform a cohort study in a larger sample. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-01011-5.

Early and delayed puberty among Iranian children with obesity.

BACKGROUND: It has been hypothesized that puberty onset is disturbed as the children gain more weight. This study aimed to investigate the prevalence and risk factors of the puberty disturbances among children with obesity in Tehran, Iran. METHODS: This study was performed as a cross-sectional study, investigating 168 children with obesity from Tehran, Iran, from March 2018 to February 2019. BMI percentile more than 95% was considered as the inclusion criteria. RESULTS: Seventy-eight (46.4%) of the assessed children were females. The mean weight, height, BMI were 89.65 (±11.01) kg, 169.88 (±8.32) centimeters and 31.13(±3.8) kg/m2, respectively. There was no difference between males and females regarding the early puberty (P=0.098), but delayed puberty was significantly higher among males (P=0.029). Our results indicated higher birth weight is associated with earlier onset of obesity in children (P=0.044). CONCLUSIONS: Our study demonstrated no association between obesity and early puberty in girls; however, boys with obesity had delayed puberty. We also found higher birth weight is associated with earlier onset of obesity, putting light on the importance of preventive interventions.

Placenta derived Mesenchymal Stem Cells transplantation in Type 1 diabetes: preliminary report of phase 1 clinical trial.

INTRODUCTION: Type 1 Diabetes Mellitus (T1DM) is an auto immune reaction against insulin secreting beta cells. Exogenous insulin administration is the only standard treatment for T1DM. However, despite tight glycemic control many patients will develop chronic life-threatening complications. Recently, stem cell transplantation has been suggested as a novel treatment for eliminating the beta cell damage and promoting their regeneration by modulating auto-immunity. To our knowledge; this is the first preliminary report of placenta derived MSCs (PLMSCs) transplantation in juvenile T1DM. METHOD: An Open label non-randomized phase 1 clinical trial was designed to evaluate the safety of PLMSCs transplantation in new onset juvenile T1DM (IRCT20171021036903N2). PLMSCs were manufactured in our clean room facility using a Xeno-free/GMP compliant protocol. The first series of patients (n = 4) received one dose of1 × 106 PLMSCs/kg intravenously. Diabetic clinical and laboratory parameters and side effects were evaluated weekly for the first month, monthly for 6 months, and then every 3 month till 1 year. RESULTS: Serious adverse events were not seen during 1 year follow-up. Partial remission and hypoglycemic attacks were happened one month after transplantation in two patients. ZnT8-Ab decreased till month 3 and then increased again in all patients. Anti Gad-Ab decreased till month 3 of follow up then increased. DISCUSSION: This preliminary report of our phase I clinical trial demonstrated the short term safety of PLMSCs transplantation in juvenile T1DM. To prove the long term safety and probable efficacy of this treatment more investigations are needed. TRIAL REGISTRATION: Iranian Registry of Clinical Trials: IRCT20171021036903N2.

Novel Treatment for Congenital Disorder of Glycosylation in a Patient with Novel Homozygote Mutation of PMM2: A Case Report and Review Literature.

BACKGROUND: In Congenital Disorder of Glycosylation (CDG) type Ia, homozygous mutations of the PMM2 gene cause phosphomannomutase 2 dysfunction. CASE PRESENTATION: Herein, a 10-month-old girl, is presented with severe hypotonia, along with inappropriately normal mental status and normal facies. High 2-ketoglutaric acid was detected in her urine, therefore, the diagnosis of 2-Ketoglutarate dehydrogenase complex (KDHC) deficiency was made for this patient. A high dose of vitamin B1 was administered because thiamine is considered a co-factor in this inborn error of metabolism. She responded very well to the daily administration of 500 mg/day vitamin B1 and stood up without help 5 months later. She had also experienced a seizure, which responded well to pyridoxine. Then, she grew up into a 3.5-years-old child who could talk and walk normally. Recently, whole-exome sequencing was performed for her, which showed homozygote mutation of PMM2, therefore, the diagnosis was changed from KDHC deficiency to PMM2-CDG. CONCLUSION: Paying attention to the pathophysiology of inborn errors of metabolism is necessary while considering the defective enzyme co-factor, which may help us to find an option for the treatment of such rare diseases.

Withdrawal Notice: MMR Vaccine Susceptibility of Viral Agents Causing Meningitis and Meningoencephalitis in Children

The article has been withdrawn from the journal "Infectious Disorders ­ Drug Targets" as it has already been found to be published in the journal in a Persian journal in the Persian language. Bentham Science apologizes to the readers of the journal for any inconvenience this may cause. The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure, or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

Antibiotic Susceptibility of Bacterial Agents Causing Meningitis in Children Older than 1 Month.

The frequency and antibiotic susceptibility of bacterial meningitis in children older than one month at Children's Medical Center during 2012-2017 were evaluated in this study. The CSF samples were cultured, and antibiotic sensitivity tests were performed. The samples were cultured on chocolate agar, blood agar (for gram positive) and Mkanky (for gram negative). The antimicrobial susceptibility of the isolates was determined using the disc diffusion method. In total, 72 samples were positive for bacterial infection where Staphylococcus epidermidis (20.8%) was seen most and Enterobacter (1.4%) and Pseudomonas aeruginosa (1.4%) was seen least. Most of these patients were under 1 year of the age and overall frequency of positive cultures of CSF in men (58.3%) was greater than women (41.7%). Bacterial meningitis has relatively diverse etiological factors that include; time of infection, geographical location and age. Most commonly seen bacteria were Staphylococcus aureus with S.epidermidis whereas, Escherichia coli and Pseudomonas aeruginosa was seen least. This result can be substantial in hospitalized patients, because these bacteria are also the result of nosocomial infections.

Pericentric Inversion of Chromosome 9 in an Infant With Ambiguous Genitalia.

Pericentric inversion of Chromosome 9 is one of the most common chromosomal abnormalities, which could be associated with various manifestations in some cases. Herein, a patient is presented with ambiguous genitalia that karyotyping revealed pericentric inversion of Chromosome 9 (p12,q13). Pericentric inversion of Chromosome 9 could be considered in the list of differential diagnosis of those with ambiguous genitalia, while chromosomal karyotype and culture could be recommended in children with ambiguous genitalia.

Caustic Agent Ingestion by a 1.5-Year-Old Boy.

We present a case of caustic ingestion by a 1.5-year-old boy. The caustic agent was drain opener which is a strong alkaline substance. Children in Iran and many other countries are still exposed to not "child proof" (child resistant packaging) toxic substance containers. Ingestion of caustic agents may lead to necrosis, perforation, and strictures. Substances that are ingested more frequently are liquid alkali material which causes severe, deep liquefaction necrosis. Common signs and symptoms of caustic agents are vomiting, drooling, refusal to drink, oral burns, stridor, hematemesis, dyspnea, dysphagia and abdominal pain. Even if no oropharyngeal lesion is seen, a significant esophageal injury which can lead to perforation and stricture cannot be ruled out. If abdominal pain or rigidity, substernal, chest or back pain exists, visceral perforation should be considered. The first thing to be checked is airway assessment. A lot of patients should be admitted to intensive care unit, and endoscopic evaluation, surgical intervention, long-term hospitalization, and worsening quality of life or among the complications. Preventive measures especially at the country level and approving proper legislation for obligating the related industries to produce child proof containers for house hold toxic products are the urgent measures to be followed by all of us.

Red flags of organic recurrent abdominal pain in children: study on 100 subjects.

OBJECTIVE: A variety of sign, symptoms and laboratory findings are more common in children with organic abdominal pains. This study was performed to evaluate the prevalence of organic and functional abdominal pains and relation of red flags to organic pains in 100 children with recurrent abdominal pain (RAP). METHODS: One hundred consecutive patients with RAP were enrolled in the study. A complete interview and physical examination was made for each patient, accompanied by a series of laboratory, clinical and para-clinical examinations. The data were recorded and analyzed. Logistic regression analysis was used to model and formulize correlations between sign, symptoms, and laboratory findings with organic and functional abdominal pain. FINDINGS: Among 100 patients (52% male, 48% female, Age: 9.29±3.17) diagnostic works up revealed organic pain for 57 patients. The most common symptoms of the patients included constipation, diarrhea, chest pain, cough, headache, vomiting, hematuria, and dysuria. Fecal incontinence, delayed puberty, organomegaly, jaundice, and family history of inflammatory bowel disease were reported in none of the patients with RAP. Fever, pain not located in periumbilical area, nocturnal pain, elevated erythrocyte sedimentation rate, weight loss, growth disorder, and abdominal tenderness were among the red flags which revealed diagnosis of organic pain in this study. CONCLUSION: A series of red flags could increase likelihood of finding organic pain in children with RAP.