Clinical heterogeneity of dominant chronic mucocutaneous candidiasis disease: presenting as treatment-resistant candidiasis and chronic lung disease.

In gain-of-function STAT1 mutations, chronic mucocutaneous candidiasis disease (CMCD) represents the phenotypic manifestation of a complex immunodeficiency characterized by clinical and immunological heterogeneity. We aimed to study clinical manifestations, long-term complications, molecular basis, and immune profile of patients with dominant CMCD. We identified nine patients with heterozygous mutations in STAT1, including novel amino acid substitutions (L283M, L351F, L400V). High risk of azole-resistance was observed, particularly when intermittent regimens of antifungal treatment or use of suboptimal dosage occurs. We report a case of Cryptococcosis and various bacterial and viral infections. Risk of developing bronchiectasis in early childhood or gradually evolving to chronic lung disease in adolescent or adult ages emerges. Lymphopenia is variable, likely progressing by adulthood. We conclude that continuous antifungal prophylaxis associated to drug monitoring might prevent resistance to treatment; prompt diagnosis and therapy of lung disease might control long-term progression; careful monitoring of lymphopenia-related infections might improve prognosis.

Endocrine and metabolic disorders in adolescent and adult patients born small for gestational age.

Children born small for gestational age (SGA), defined by a birth weight and/or length standard deviation score (SDS) of < -2 based on an appropriate reference population, represent a diverse group due to multiple underlying causes of reduced growth. This classification results in a heterogeneous patient cohort. SGA children are prone to endocrinological and metabolic issues not only in childhood but also extending into adolescence and adulthood. This population faces elevated health risks, including persistent short stature, premature adrenarche, pubertal development alterations, neurocognitive problems, and metabolic syndrome. Insulin resistance emerges as a pivotal factor c nht6j7ikontributing to these metabolic complications, prominently featuring obesity, insulin resistance, hypertension, and an increased risk of type 2 diabetes mellitus in adulthood. These medium- to long-term complications significantly impact their quality of life. Growth hormone (GH) therapy for short children born SGA facilitates height normalization throughout childhood, adolescence, and into adulthood. Catch-up growth, however, correlates with heightened risks of obesity, insulin resistance, and metabolic syndrome. Conversely, those without catch-up growth tend to exhibit pronounced short stature and cognitive dysfunction. Given these determinants, comprehensive management and clinical monitoring of SGA children should commence in the neonatal period and extend into adulthood. Recognizing and addressing these challenges early in life can mitigate the long-term impact on health and well-being, emphasizing the importance of a lifelong approach to their care.

Preliminary epidemiological analysis on children and adolescents with novel coronavirus disease (2019-nCoV) in a central area of Calabria region.

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Hashimoto encephalopathy: a case report and a short revision of current literature.

Hashimoto encephalopathy (HE) is a rare but controversial entity encompassing a variety of neuropsychological presentations in the setting of autoimmune thyroid disease. HE, mostly described in adults, with a female­to­male ratio of 4:1, is a relatively rare entity in the pediatric population and probably under recognized as a cause of acute encephalopathy in children and adolescents. A number of pathogenetic mechanisms have been suggested. Female prevalence, presence of autoantibodies, fluctuating course, and response to immunomodulatory therapy suggest the autoimmune nature of the disease. Existing diagnostic criteria for adults require modification to be applied to children and adolescents, who differ from adults in their clinical presentations, clinical findings, autoantibody profiles, treatment response, and long-term outcomes. A combination of neurological findings, positive antithyroid autoantibodies, and responsiveness to steroids is diagnostic of HE. We add a new case of HE in an adolescent girl and review the current HE literature.

Screening of COVID-19 in children admitted to the hospital for acute problems: preliminary data.

BACKGROUND: The new Coronavirus identified in Whuan at the end of 2019 (SARS-CoV-2) belongs to the Beta Coronavirus genus and is responsible for the new Coronavirus 2019 pandemia (COVID-19). Infected children may be asymptomatic or present fever, dry cough, fatigue or gastrointestinal symptoms. The CDC recommends that clinicians should decide to test patients based on the presence of signs and symptoms compatible with COVID-19. MATERIAL AND METHODS: 42 children (the majority < 5 years of age) were referred, to our Pediatric Department, as possible cases of COVID-19 infection. Blood analysis, chest X-ray, and naso-oropharyngeal swab specimens for viral identification of COVID-19 were requested. RESULTS: None of the screened children resulted positive for COVID-19 infection. At first presentation, the most frequent signs and symptoms were: fever (71.4%), fatigue (35.7%) and cough (30.9%).  An  high  C-reactive protein value and abnormalities of chest  X-ray (bronchial wall thickening) were detected in 26.2% and 19% of patients, respectively. Almost half of patients (45.2%) required hospitalization in our Pediatric Unit and one patient in Intensive Care Unit. CONCLUSIONS: Testing people who meet the COVID-19 suspected case definition criteria is essential for clinical management and outbreak control. Children of all ages can get COVID-19, although they appear to be affected less frequently than adults, as reported in our preliminary survey. Further studies are needed to confirm our observations.

Genetic variants associated with Fabry disease progression despite enzyme replacement therapy.

Enzyme replacement therapy (ERT) has been widely used for the treatment of Fabry disease, a rare X-linked recessive disorder due to absent or reduced activity of lysosomal enzyme α-galactosidase A. It is still unclear why some patients under ERT show disease progression typically with renal, cardiovascular and cerebrovascular dysfunctions. Here, we investigated the involvement of drug absorption, distribution, metabolism, and excretion gene variants in response variability to ERT, genotyping 37 patients with the Affymetrix Drug Metabolizing Enzyme and Transporters (DMET) Plus microarray. We found three single nucleotide polymorphisms in human alcohol dehydrogenase (ADH)4 gene (rs1126670, rs1126671, rs2032349) and one in ADH5 gene (rs2602836) associated with disease progression (p < 0.05). Our data provide a basic tool for identification of patient with ERT non-response risk that may represent a framework for personalized treatment of this rare disease.

Gastrointestinal Symptoms of Patients with Fabry Disease.

In order to characterize gastrointestinal (GI) symptoms of 50 patients with Fabry disease (FD) (22 M; age range: 4-70 y; 35 adults and 15 children), validated questionnaires of GI symptoms were used to diagnose the functional gastrointestinal disorders (FGIDs) of the patients with GI symptoms (33/50 (66%); 25/35 adults and 8/15 children) according to Rome III criteria. In 16/25 of these adults and 2/8 of these children, the symptoms mimicked FGID. The adult subgroup included patients with unspecified functional bowel disorder (n = 9), functional bloating (n = 7), and IBS (n = 5), and the child subgroup included patients with abdominal migraine (n = 1) and IBS (n = 1). Among the 25 adults, 14 reported feeling full after a regular-size meal, and 12 complained of abdominal bloating/distension. All of the children with GI symptoms complained of low abdominal pain associated with changes in the form of the stool/improvements with defecation. In conclusion, according to Rome III criteria, the most frequent diagnoses of FGID among the adults with FD were unspecified functional bowel disorder, followed by functional bloating and IBS. The most frequent GI symptom in the children in our population was IBS-like abdominal pain, while the adults exhibited a full feeling following a regular-size meal and abdominal bloating/distension.

Clinical and immunological data of nine patients with chronic mucocutaneous candidiasis disease.

This paper describes the heterogeneous clinical phenotype of a cohort of nine patients diagnosed with heterozygous mutations in STAT1. We report data of extended immunophenotyping over time and we show lung damage in four patients. The increased phosphorylation of STAT1 in response to IFNγ and IFNα stimulation proves the gain-of-function nature of the defects. The data are supplemental to our original article concurrently published "Clinical heterogeneity of dominant chronic mucocutaneous candidiasis disease: presenting as treatment-resistant candidiasis and chronic lung disease" [1], where additional results and interpretation of our research can be found.

Genetic variants associated with gastrointestinal symptoms in Fabry disease.

Gastrointestinal symptoms (GIS) are often among the earliest presenting events in Fabry disease (FD), an X-linked lysosomal disorder caused by the deficiency of α-galactosidase A. Despite recent advances in clinical and molecular characterization of FD, the pathophysiology of the GIS is still poorly understood. To shed light either on differential clinical presentation or on intervariability of GIS in FD, we genotyped 1936 genetic markers across 231 genes that encode for drug-metabolizing enzymes and drug transport proteins in 49 FD patients, using the DMET Plus platform. All nine single nucleotide polymorphisms (SNPs) mapped within four genes showed statistically significant differences in genotype frequencies between FD patients who experienced GIS and patients without GIS: ABCB11 (odd ratio (OR) = 18.07, P = 0,0019; OR = 8.21, P = 0,0083; OR=8.21, P = 0,0083; OR = 8.21, P = 0,0083),SLCO1B1 (OR = 9.23, P = 0,0065; OR = 5.08, P = 0,0289; OR = 8.21, P = 0,0083), NR1I3 (OR = 5.40, P = 0,0191) and ABCC5 (OR = 14.44, P = 0,0060). This is the first study that investigates the relationships between genetic heterogeneity in drug absorption, distribution, metabolism and excretion (ADME) related genes and GIS in FD. Our findings provide a novel genetic variant framework which warrants further investigation for precision medicine in FD.

The definition of abstinence.

A teen's definition of sexual activity most often does not include oral or anal sex. Abstinence only programs vary widely as to how they define sexual behavior and may be contributing to misinformation about STD transmission. Unknown is the extent to which declining teen pregnancy rates are due to non-coital activities replacing vaginal intercourse.