The real-life management of glucose homeostasis abnormalities in pediatric onco-hematological diseases: data from a national survey.

Glycemic abnormalities are a frequent finding in pediatric oncological patients, both during treatment and after its discontinuation. Moreover, impaired glucose tolerance (IGT), impaired fasting glycemia (IFG) and diabetes mellitus (DM) are not rarely diagnosed in non-oncological hematological diseases. To explore the current pediatric Italian approach to the diagnosis and the management of the glycemic alterations in this clinical setting and, thus, to identify and enforce current clinical needs, we submitted an online 23-items survey to all the Italian Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) centers, and surveys were descriptively analyzed. Thirty-nine AIEOP centers were involved in the study. In 2021, among 75278 children and adolescents affected by an oncological or a hematological disease, 1.2 and 0.65% developed DM, while IGT or IFG were widespread in 2.3 and 2.8%, respectively. The main causes of DM were the use of corticosteroids in patients with cancer and the iron overload in patients with thalassemia. Venous fasting plasma glycemia was the most used tool to detect glycemic abnormalities. The performance of oral glucose tolerance test (OGTT) was extremely limited, except when IFG occurred. Despite the diagnosis of DM, ∼45% of patients with cancer and 30% of patients with one hematological disease did not receive an appropriate treatment. In the other cases, insulin was the drug of first choice. Emerging technologies for diabetes care (glucose sensors and insulin pumps) are not largely used yet. The results of our study support the standardization of the care of the glycemic abnormalities during or after onco-hematologic diseases in the pediatric age. Despite the scarce data in pediatric literature, proper guidelines are needed.

A Very Early Diagnosis of Complete Androgen Insensitivity Syndrome Due to a Novel Variant in the AR Gene: A Neonatal Case Study.

Androgen insensitivity syndrome (AIS) is one of the most common Disorders of Sexual Differentiation (DSDs). AIS is characterized by an X-linked recessive inheritance pattern associated with variants in the androgen receptor (AR) gene that affects the masculinization process in individuals with XY karyotype. Here, we report a neonatal case of a very early diagnosis of complete AIS due to a novel variant in the AR gene. In the present case, after the clinical evaluation, the infant has undergone the following tests: biochemical analyses, including newborn screening workflow, karyotype analysis, and Next-Generation Sequencing (NGS) panel of 50 genes involved in DSDs. The NGS analysis identified a missense variant, c.2108C>A, in the AR gene. According to a cytogenetic analysis, the patient presented a 46, XY karyotype, thus the resulting hemizygote for the AR gene variant. The variant is not currently described in the literature nor in the ClinVar database. However, according to computational models, the variant could have a pathogenetic effect. This clinical case reveals a novel variant of the AR gene with a possible pathogenetic effect associated with AIS and highlights the importance of a multidisciplinary approach for the timely diagnosis and appropriate follow-up of the patient.

Future acceptance of automated insulin delivery systems in youths with type 1 diabetes: validation of the Italian artificial pancreas-acceptance measure.

AIM: The purpose of this study was to develop a questionnaire to examine the future acceptance of Automatic insulin delivery systems (AIDs), their perceived usefulness, ease of use, and trust in the device in subjects with type 1 diabetes (T1D). METHODS: A questionnaire in Italian, based on the Technology Acceptance Model, was developed to examine intention to use AIDs, considered as a measure of future acceptance, and its determinants to use the system. A total of 43 questions for children and 46 for parents were included, and a 5-point Likert scale was used. RESULTS: 239 subjects with T1D using multiple daily injections (MDI) or sensor-augmented pump (SAP) and their parents completed the questionnaire. The completion rate was excellent, with almost 100% of items answered. The overall Cronbach's coefficient for children and adolescents was 0.92 and 0.93 for parents, indicating excellent internal consistency in both groups. Parent-youth agreement was 0.699 (95% confidence interval: 0.689-0.709), indicating a good agreement between the two evaluations. Factor analysis identified measurement factors for the "artificial pancreas (AP)-acceptance labeled benefits and hassles of AIDs, and the internal consistency of the total scale was alpha = 0.94 for subjects with T1D and 0.95 for parents. The level of AP acceptance was more than neutral: 3.91 ± 0.47 and 3.99 ± 0.43 (p = 0.07) for youths and parents, respectively (possible score range 1 to 5, neutral score is 3.0). Parents reported higher scores in the benefit items than children-adolescents (p = 0.04). CONCLUSIONS: We developed a new questionnaire based on the items available in the literature, and we demonstrated that the "AP-acceptance" reveals a meaningful factor structure, good internal reliability, and agreement between parent-young people evaluations. This measure could be a valuable resource for clinicians and researchers to assess AP acceptance in pediatric patients with T1D and their parents. This patient profiling approach could help to enroll candidates for AIDs with proper expectations and who most likely will benefit from the system.

Growth plate extracellular matrix defects and short stature in children.

Many etiological factors causing short stature have already been identified in humans. In the last few years, the advent of new techniques for the detection of chromosomal and molecular abnormalities has made it possible to better identify patients with genetic causes of growth failure. Some of these factors directly affect the development and growth of the skeleton, since they damage the epiphyseal growth plate, where linear growth occurs, influencing chondrogenesis. In particular, defects in genes involved in the organization and function of the growth plate are responsible for several well-known conditions with short stature. These genes play a pivotal role in various mechanisms involving the extracellular matrix, intracellular signaling, paracrine signaling, endocrine signaling, and epigenetic regulation. In this review, we will discuss the genes involved in extracellular matrix disorders. The identification of genetic defects in linear growth failure is important for clinicians and researchers in order to improve the care of children affected by growth disorders.

Increased hepcidin levels and non-alcoholic fatty liver disease in obese prepubertal children: a further piece to the complex puzzle of metabolic derangements.

INTRODUCTION: Several studies on obese youths and adults have reported increased hepcidin levels, which seems to be related to metabolic and iron metabolism alterations. The complete mechanisms involved in hepcidin increase remain to be elucidated, and particularly its role in the development of other known complications such as Nonalcoholic Fatty Liver Disease (NAFLD). NAFLD in prepubertal children might be of special interest in understanding the underlying mechanisms. METHODS: Anthropometric measurements, liver ultrasonography, lipid profile, liver function, oxidative stress, inflammatory state, and iron metabolism were studied in 42 obese prepubertal children and 33 healthy controls. We, therefore, evaluated the presence of possible correlations between Hepcidin and the other metabolic variables, and the possible association between NAFLD and iron metabolism. RESULTS: Hepcidin levels were significantly increased in the obese prepubertal children (p=0.001) with significant differences between obese children with and without NAFLD (p=0.01). Blood iron was lower in obese children (p=0.009). In the obese group, a negative correlation between hepcidin and both blood iron levels (p=0.01) and LagPHASE (p=0.02) was found. In addition, a positive association between hepcidin and NAFLD (p=0.03) was detected. CONCLUSIONS: We suggest that an increase in hepcidin levels may represent an early step in iron metabolism derangements and metabolic alterations, including NAFLD, in prepubertal obese children.

A Novel Heterozygous Mutation of the CYP17A1 Gene in a Child with a Micropenis and Isolated 17,20-Lyase Deficiency.

Disorders of sexual development (DSDs) are characterized by a heterogeneous group of congenital conditions associated with atypical development of the sex chromosomes, gonadal or anatomical sex. We report the case of a child with an isolated micropenis, a typical feature of the 46,XY DSD showing low basal testosterone levels and post-stimulation with the hCG test. Molecular analysis using a next-generation sequencing (NGS) panel of 50 genes involved in DSDs was performed, revealing a heterozygous mutation, c.1040G > ANM_000102.4, in the CYP17A1 gene. Sanger sequencing was used to confirm the gene variant detected by NGS; it was also performed to his parents, revealing the presence of the same mutation in the mother, who presented no features of the disease. Then, the serum steroid profile was determined by liquid chromatography coupled to tandem mass spectrometry analysis. Interestingly, this analysis highlighted low levels of testosterone, progesterone, and dehydroepiandrostenedione, as also confirmed by a stimulus test with ACTH. These results suggest that, in some cases, heterozygous mutations in recessive genes involved in adrenal steroidogenesis can also affect the patient's phenotype.