Evaluation of ovarian reserve in young females with non-iatrogenic ovarian insufficiency to establish criteria for ovarian tissue cryopreservation.

RESEARCH QUESTION: Can ovarian reserve parameters predict the outcome of ovarian tissue cryopreservation (OTCP) in patients ≤18 years with non-iatrogenic premature ovarian insufficiency (POI)? DESIGN: Retrospective cohort analysis carried out in a single tertiary hospital between August 2010 and January 2020. Thirty-seven patients ≤18 years with non-iatrogenic POI (27 with Turner syndrome, six with POI of unknown aetiology, three with galactosemia and one with blepharophimosis, ptosis, epicanthus inversus syndrome) were included. Three parameters were used to evaluate ovarian reserve: anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH) and transabdominal antral follicle count. Fertility preservation (most commonly OTCP) was offered if ovarian reserve was diminished and one or more parameters was positive. Follicles were counted in ovarian samples obtained at the time of OTCP. RESULTS: Ovarian reserve was diminished in 34 patients and 19 of them had one or more positive parameter. Fourteen (11 aged ≥12 years and 3 aged <12) underwent OTCP, one (14 years old) underwent ovarian stimulation and oocyte cryopreservation and four declined fertility preservation. Follicles were detected in 11 of 14 patients who underwent OTCP with one or more positive parameters (79%), and in all those (100%) who had two or three positive parameters. The median number of follicles was 27 (range 5-64) and 48 (range 21-75) in patients ≥12 years and those <12 years, respectively. CONCLUSION: This study shows that if OTCP is performed in patients with one or more positive parameters of ovarian activity, a 79% positive predictive value is achieved for the detection of follicles. The incorporation of this criterion for OTCP will minimize the risk of harvesting ovarian tissue with a low number of follicles.

Fatty acid-binding protein 4: a key regulator of ketoacidosis in new-onset type 1 diabetes.

AIMS/HYPOTHESIS: Fatty acid-binding protein 4 (FABP4) is an adipokine with a key regulatory role in glucose and lipid metabolism. We prospectively evaluated the role of FABP4 in the pathophysiology of diabetic ketoacidosis (DKA) in new-onset type 1 diabetes. METHODS: Clinical and laboratory data were prospectively collected from consecutive children presenting with new-onset type 1 diabetes. In addition to blood chemistry and gases, insulin, C-peptide, serum FABP4 and NEFA were collected upon presentation and 48 h after initiation of insulin treatment. In a mouse model of type 1 diabetes, glucose, insulin, ß-hydroxybutyrate and weight were compared between FABP4 knockout (Fabp4-/-) and wild-type (WT) mice. RESULTS: Included were 33 children (mean age 9.3 ± 3.5 years, 52% male), of whom 14 (42%) presented with DKA. FABP4 levels were higher in the DKA group compared with the non-DKA group (median [IQR] 10.1 [7.9-14.2] ng/ml vs 6.3 [3.9-7] ng/ml, respectively; p = 0.005). The FABP4 level was positively correlated with HbA1c at presentation and inversely correlated with venous blood pH and bicarbonate levels (p < 0.05 for all). Following initiation of insulin therapy, a marked reduction in FABP4 was observed in all children. An FABP4 level of 7.22 ng/ml had a sensitivity of 86% and a specificity of 78% for the diagnosis of DKA, with an area under the receiver operating characteristic curve of 0.78 (95% CI 0.6, 0.95; p = 0.008). In a streptozotocin-induced diabetes mouse model, Fabp4-/- mice exhibited marked hypoinsulinaemia and hyperglycaemia similar to WT mice but displayed no significant increase in ß-hydroxybutyrate and were protected from ketoacidosis. CONCLUSIONS/INTERPRETATION: FABP4 is suggested to be a necessary regulator of ketogenesis in insulin-deficient states.

Diabetes Out-of-the-Box: Diabetes Mellitus and Impairment in Hearing and Vision.

PURPOSEOF REVIEW: This review aims to provide an update on the etiologies of diabetes that are due to genetic disorders and that co-occur with impaired hearing or vision and to compare them. The potential mechanisms, including novel treatments, will be detailed. RECENT FINDINGS: Wolfram syndrome, Kearns-Sayre syndrome, thiamine-responsive megaloblastic anemia, and maternally inherited diabetes and deafness are genetic disorders characterized by diabetes, impaired hearing, and vision. They differ in mode of inheritance, age at presentation, and the involvement of other organs; they are often misdiagnosed as type 1 or type 2 diabetes. Suspicion of a genetic diabetes syndrome should be raised when pancreatic autoantibodies are negative, other organs are involved, and family history includes diabetes. Correct diagnosis of the various syndromes is important for tailoring the most advanced treatment, preventing disease progression, and enabling proper genetic counseling.

Female fragile X premutation carriers are at increased risk for metabolic syndrome from early adulthood.

BACKGROUND AND AIMS: Women with primary ovarian insufficiency exhibit an unfavorable cardiovascular risk profile. A common cause for primary ovarian insufficiency is fragile X premutation (FXPC), and data on the cardiovascular risk factors in women with FXPC are scarce. We aimed to assess the prevalences of abnormal metabolic components among FXPC. METHODS AND RESULTS: Clinical, anthropometric and laboratory data were collected from 71 women with FXPC and compared to 78 women referred for counseling in an in-vitro fertilization clinic (control group). The mean ± SD ages of the FXPC and control groups were 33.5 ± 5.6 and 36.2 ± 5.3 years, respectively (p = 0.003). In a logistic regression analysis, the FXPC group had increased risks for hyperglycemia, hypertriglyceridemia, central obesity and low high-density lipoprotein cholesterol, of 21.8-fold (95% CI 2.7-175, p = 0.004), 6.9-fold (95% CI 2.5-18.7, p < 0.0001), 3.1-fold (95% CI 1.4-6.9, p = 0.005) and 2.4-fold (95% CI 1.1-5.2, p = 0.03), compared to the control group. The FXPC group had 2.7-fold higher prevalence of two abnormal metabolic components; 19% met the full criteria of MetS, compared to 3% of the control group. Neither CGG repeats nor ovarian reserve markers were associated with metabolic risk. CONCLUSIONS: Carriers of fragile X premutation are at increased metabolic risk from early adulthood; waist circumference, glucose and lipid levels are particularly elevated. We recommend metabolic screening for all women with FMR1 premutation, to enable early interventions for prevention of long-term cardiovascular comorbidities.

Dual diagnosis of type 1 diabetes mellitus and attention deficit hyperactivity disorder.

BACKGROUND: Data regarding glycemic control in children and adolescents with a dual diagnosis of type 1 diabetes mellitus (T1DM) and attention-deficit/hyperactivity disorder (ADHD) are limited. OBJECTIVE: To compare various aspects of diabetes control among youth with T1DM, between those with and without ADHD. METHODS: In this cross-sectional study of youth with T1DM, 39 had ADHD (mean age 14.1 ± 2.8 years) and 82 did not (control group, mean age 12.6 ± 3.3 years). Health-related quality of life was assessed by a Diabetes Quality of Life (DQOL) questionnaire submitted to their parents. Glycemic data were downloaded from glucometers, pumps, and continuous glucose monitoring systems. HbA1c levels, hospitalizations, and severe hypoglycemic and diabetes ketoacidosis events were retrieved from the medical files. RESULTS: Compared to the control group mean HbA1c level of the ADHD group was higher: 8.3 ± 1.1% versus 7.7 ± 1.0% (p = 0.005) and the percent of time that glucose level was in the target range (70-180 mg/dl) was lower: 48 ± 17% versus 59 ± 14% (p = 0.006). Mean glucose and glucose variability were higher in the ADHD group. Youth with ADHD who were not pharmacologically treated had worse HbA1c and more hospitalizations than those who were treated. DQOL did not differ between the control group, the treated ADHD group, and the untreated ADHD-Group. CONCLUSIONS: Dual diagnosis of T1DM and ADHD during childhood leads to worse diabetes control, which is more pronounced in the context of untreated ADHD. Healthcare providers should be aware of the difficulties facing youth with T1DM and ADHD in coping with the current intensive treatment of diabetes.

Kidney failure risk in type 1 vs. type 2 childhood-onset diabetes mellitus.

BACKGROUND: Diabetic kidney disease (DKD) is becoming increasingly common among children. We aimed to estimate the risk of end-stage renal disease (ESKD) and mortality among adolescents with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) and normal renal function compared with non-diabetics. We hypothesized that childhood onset T1DM vs. T2DM would be associated with a different risk profile for developing ESKD and its complications. METHODS: A nationwide, population-based, retrospective cohort study, including 1,500,522 adolescents examined for military service between 1967 and 1997, which were classified according to the presence and type of diabetes. Data were linked to the Israeli ESKD registry. Cox proportional-hazards models were used to estimate the hazard ratio (HR) for ESKD. RESULTS: At study enrolment, 1183 adolescents had T1DM and 196 had T2DM. ESKD developed in 2386 non-diabetic individuals (0.2%) compared with 72 individuals (6.1%) with T1DM and 8 individuals (4.1%) with T2DM. Participants with T1DM were younger at ESKD onset than participants with T2DM (median age, 36.0 vs. 40.5 years, P < 0.05). In a multivariate model adjusted for age, sex, paternal origin, enrollment year, BMI, and blood pressure, T1DM and T2DM were associated with HR of 36.4 (95% CI 28.3-46.9) and 19.3 (95% CI 9.6-38.8) for ESKD, respectively. Stratification according to sex, ethnicity, immigration, and socioeconomic status did not materially change the HR. During the follow-up period, mortality rates were higher in T2DM as compared with T1DM and controls (8.7 %, 2.2%, and 2.7% respectively). CONCLUSIONS: T1DM and T2DM in adolescents with normal renal function confer a significantly increased risk for ESKD. T1DM is associated with younger age at ESKD onset while T2DM is associated with higher mortality rate.

Trabecular Bone Score in Children and Adolescents With Inflammatory Bowel Diseases.

INTRODUCTION: Trabecular bone score (TBS) is a textural index that evaluates bone microarchitecture of the lumbar spine. Our aim was to assess TBS in children with inflammatory bowel diseases and to evaluate correlations with clinical, laboratory and densitometric variables. METHODS: A retrospective study of TBS and areal bone mineral density measurements by dual-energy X-ray absorptiometry (DXA) of children with either Crohn's disease (CD) or ulcerative colitis (UC). Bone mineral apparent density was calculated for size adjustment. TBS Z-score for each child were calculated based on data from a healthy population of similar age and gender distribution. Variables significantly associated with TBS were included in stepwise linear regression models to examine independent predictors of TBS. RESULTS: Fifty patients (age at DXA scan 13.8 ± 3.0 years, 29 males) were included. No significant differences were observed between the patients with CD and UC, in age at diagnosis, age at DXA scan and disease duration. The mean TBS of patients with CD (n = 35) was lower than of patients with UC (n = 15): 1.340 ± 0.080 vs 1.395 ± 0.092, p = 0.040. The mean TBS Z-score of patients with CD, -0.443 ± 0.788, was significantly lower than expected in healthy children (p = 0.002), while the mean TBS Z-score of patients with UC, 0.231 ± 0.685, was similar to that of healthy children (p = 0.212). In the stepwise linear regression analysis, BMI Z-score at diagnosis, phosphorus level at diagnosis and age at the time of the DXA scan were significant independent predictors of TBS (r²â€¯= 0.604; ß = 0.037, 95% confidence interval (CI) for ß 0.022-0.051, p < 0.001; ß = 0.045, 95% CI: 0.017-0.073, p = 0.002; and ß = 0.031, 95% CI: 0.005-0.021, p < 0.002, respectively). CONCLUSIONS: TBS is significantly reduced in pediatric patients with CD but not in patients with UC. This finding likely reflects the effect of CD on bone microarchitecture.

Increased prevalence of disordered eating in the dual diagnosis of type 1 diabetes mellitus and celiac disease.

BACKGROUND: Disordered eating behaviors (DEBs) may lead to full blown eating disorders. Both type 1 diabetes mellitus (T1DM) and celiac disease (CD) have been linked to DEBs. OBJECTIVE: To compare the presence of DEBs between adolescents and young adults with a dual diagnosis of T1DM and CD, and individuals with only one of the diagnoses. METHODS: Individuals with a dual diagnosis of T1DM and CD ("T1DM + CD group" n = 39), with a diagnosis of T1DM only ("T1DM group" n = 97) and with a diagnosis of CD only ("CD group" n = 267) filled the Eating Attitude Test-26 (EAT-26) questionnaire. Those with T1DM completed in addition to the Diabetes Eating Problem Survey-Revised (DEPS-R). RESULTS: The study population comprised of 403 individuals, of whom 65% were females. There were no statistically significant differences among the groups in distribution of sex, age, hemoglobin A1c (HbA1c) levels, age of disease diagnosis and duration. The prevalence of DEBs in the T1DM + CD group was 3-fold higher (26.0%) than in the T1DM (8.2%) and CD (8.2%) groups (P = .003). This trend was observed for both females and males. Multivariate analysis demonstrated that the T1DM + CD group had an increased risk for DEBs (odds ratio, OR: 4.7, 95% confidence interval, CI: 1.9-11.2, P = .001) after adjustment for age, sex, and body mass index. Additionally, being female, older and overweight increased the risk for DEBs. HbA1c values were not associated with an increased DEBs rate. CONCLUSIONS: Individuals with the dual diagnoses of T1DM and CD have an increased likelihood to develop DEBs compared to those with only one of these diagnoses.

[FROM GENETICS OF FRAGILE X SYNDROME TO DEVELOPMENT OF TARGETED AND PERSONALIZED DRUG THERAPY].

INTRODUCTION: At the end of the last century Fragile X syndrome was identified, and the main syndrome characteristics were discovered. The syndrome is caused from a flaw in the number of nucleotide repeats that encodes for a regulatory protein which is critical for neural connectivity and normal brain development. The syndrome is characterized by neurodevelopmental and intellectual disabilities, autism spectrum features and other clinical features associated with the same gene aberration. The number of trinucleotide repeats have a direct effect on the outcome and the need for genetic counseling. We advocate performing genetic tests for every child with developmental delay, learning disabilities, autism spectrum disorders and especially, intellectual impairment. It is also advisable to check the number of nucleotide repeats of the gene, in every woman suffering from infertility or early menopause. In addition, genetic testing should be performed on older adults manifesting early symptoms of Parkinson's disease, balance instability, tremor or cognitive dysfunction with unknown etiology. Due to the tremendous progress in understanding the biological mechanisms of the syndrome, new molecules/drugs have been proposed and are tested, in order to find a way to bypass the defect mechanism underlying the disorder. We will review the most commonly used drugs in the treatment of Fragile X syndrome and many medications that are currently under investigation as a more targeted treatment.

[FMR1 PREMUTATION CARRIERS - ARE THEY REALLY ASYMPTOMATIC?]

INTRODUCTION: Fragile X Syndrome (FXS), the most common form of inherited mental retardation, is caused by a trinucleotide repeat expansion (CGG) in the 5'-untranslated region of the Fragile X Mental Retardation 1 (FMR1) gene located at Xq27.3. Patients with fragile X -related mental retardation, carry the full mutation CGG-repeat expansions (>200 CGG repeats), which are generally accompanied by hypermethylation of the promoter region, with the consequent transcriptional silencing of the FMR1 gene and absence of the encoded FMR1 protein (FMRP). Expansion of the CGG triplet number above the normal range (n=5-54) towards the so-called premutation status (n=55-199) is associated with increased risk for Fragile X-Associated Premature Ovarian Insufficiency (FXPOI) in females and Fragile X-Associated Tremor/ Ataxia Syndrome (FXTAS) predominantly in males. In addition, premutation women carriers are at increased risk for learning disabilities, as well as psychologic, endocrine, autoimmune and metabolic disorders. The observation that premutation carriers, both males and females, have increased FMR1 transcript levels, led researchers to suggest a similar molecular pathogenesis in both FXPOI and FXTAS. Two models have been proposed as the culprits of FXTAS and FXPOI: The toxic RNA gain-of-function model and the Repeat Associated Non-AUG initiated (RAN) translation protein toxicity model. The Fragile X Multidisciplinary Center in Sheba Medical Center, at Tel Hashomer includes a team of geneticists, fertility specialists, endocrinologists, psychologists and neurologists who work together in order to provide early detection of FMR1 premutation carriers and offer FMR1 premutation carriers and their families adequate multidisciplinary medical consultation, follow-up and care.

Fragile X Premutation Carrier Epidemiology and Symptomatology in Israel-Results from a Tertiary Child Developmental Center.

Fragile X syndrome (FXS) is the most prevalent known genetically inherited cause for autism and intellectual disability. Premutation state can cause several clinical disorders as well. We aimed to perform a nesting approach to acquire data with regard to first degree relatives of index fragile X cases at the largest child development center in Israel in order to map characteristics of Israeli FXS permutation women carriers. Seventy-nine women were referred due to a related fragile X syndrome patient, mainly an offspring or sibling. General information regarding demographics, ethnicity, and associated medical conditions were collected using interviews and structured questionnaires. Thirteen (17 %) of the women who were referred as "carrier" were proven to be actually full mutation. The mean years of education were 14 (±1.51, range 12-17). Twenty-one women (27 %) originated from Tunisia (mainly from the island of Djerba). Ten women (13 %) reported delivery of their affected offspring beyond 41 gestational weeks. Twenty-two percent of women with premutation reported symptoms consistent with learning difficulties, mainly dyscalculia, and 14 % reported ADHD symptoms. Awareness about clinical disorders of the carriers was existent only in 25 % of the patients. Increased awareness and knowledge dissemination concerning premutation symptomatology and associated medical conditions are warranted. We suggest a national registry to be installed in different countries in order to identify fragile X premutation carriers at increased risk for various medical complications.

A link between human papilloma virus vaccination and primary ovarian insufficiency: current analysis.

PURPOSE OF REVIEW: The cause of primary ovarian insufficiency (POI) is multifactorial. Known causes include external factors such as chemotherapy, radiotherapy, exposure to endocrine-disrupting chemicals, infections that lead to a permanent insult to the ovary, autoimmune conditions, and genetic causes. An association between the quadrivalent antihuman papilloma vaccine (HPV4) and POI was recently suggested. RECENT FINDINGS: An increasing number of cases of POI post-HPV4 are being reported. Possible mechanisms for the suspected effect of HPV on female reproductive function are a toxic effect or an autoimmune response. The trigger could be the vaccine immunogen contents or the adjuvants, the latter are used to increase the immune reaction. The adjuvant in HPV4 contains aluminum. Animal models have shown aluminum exposure to inhibit expression of female reproductive hormones and to induce histologic changes in the ovaries. Specific genetic compositions may be more susceptible to developing an autoinflammatory syndrome after exposure to an environmental factor. SUMMARY: The mechanisms responsible for POI are not yet fully understood. Although case reports cannot establish causation, awareness of a possible link between HPV4 and POI will help to identify and manage future cases that may arise.

Virtual reality's impact on children with type 1 diabetes: a proof-of-concept randomized cross-over trial on anxiety, pain, adherence, and glycemic control.

AIMS:  Assess the effectiveness of virtual reality (VR) technology, in reducing pain and anxiety, and improving adherence and glycemic control among children with type 1 diabetes (T1D). METHODS: Children with T1D, managed with continuous glucose monitoring and insulin pumps, were recruited for a randomized cross-over trial. Children were randomized to one of two interventions for diabetes management: group 1 used VR glasses first and group 2 listened to vocal-guided affective imagery first (audio). After 1 month, the interventions were crossed over. The outcome measures included pain and anxiety assessment, adherence, glycemic control, and patient-reported outcome measures (PROMs) of VR satisfaction and effectiveness. RESULTS:  Forty children, mean age 11.4 ± 1.8 years, were participated. During the VR part, the monthly mean pain score compared to the baseline improved in both groups by 30% (p = 0.03). A 14% reduction in the state anxiety score was observed from baseline to 1 month in both groups (p = 0.009). Glycemic control measures including time in range, time above range, and glucose management indicator improved in both groups during VR part (p < 0.004 for all), compared to audio part. After one month, the patient-reported outcome measure (PROM) of satisfaction and effectiveness was sixfold higher after 1 month in group 1 compared to group 2 (p = 0.002). Adherence improved for both groups. CONCLUSIONS: VR was shown to be effective in reducing pain and anxiety, improving adherence, PROM, and glycemic control among children with T1D. We suggest incorporating VR technology in pediatric diabetes clinics to facilitate and improve coping and management of diabetes. TRIAL REGISTRATION: Trial registration number and date of registration for prospectively registered trials:ClinicalTrials.gov Identifier: NCT05883267, May 10th, 2023.

Real-Life Achievements of MiniMed 780G Advanced Closed-Loop System in Youth with Type 1 Diabetes: AWeSoMe Study Group Multicenter Prospective Trial.

Background: We assessed real-life glycemic outcomes and predictors of composite measures of optimal glycemic control in children and adolescents with type 1 diabetes (T1D) during their initial 12 months of the MiniMed™ 780G use. Methods: This prospective observational multicenter study collected demographic, clinical, and 2-week 780G system data at five time points. Optimal glycemic control was defined as a composite glycemic control (CGC) score requiring the attainment of four recommended continuous glucose monitoring (CGM) targets, as well as the glycemia risk index (GRI) of hypoglycemia and hyperglycemia and composite CGM index (COGI). Outcome measures included longitudinal changes in multiple glycemic parameters and CGC, GRI, and COGI scores, as well as predictors of these optimal measures. Results: The cohort included 93 children, 43% girls, with a median age of 15.1 years (interquartile range [IQR] 12.9,17.0). A longitudinal analysis adjusted for age and socioeconomic index yielded a significant improvement in glycemic control for the entire cohort (ptime < 0.001) after the transition to 780G. The mean hemoglobin A1c (HbA1c) (SE) was 8.65% (0.12) at baseline and dropped by >1% after 1 year to 7.54% (0.14) (ptime < 0.001). Optimal glycemic control measures improved at 12 months post 780G; CGC improved by 5.6-fold (P < 0.001) and was attained by 24% of the participants, the GRI score improved by 10-fold (P = 0.009) and was achieved by 10% of them, and the COGI improved by 7.6-fold (P < 0.001) and was attained by 20% of them. Lower baseline HbA1c levels and increased adherence to Advanced Hybrid Closed-Loop (AHCL) usage were predictors of achieving optimal glycemic control. Conclusions: The AHCL 780G system enhances glycemic control in children and adolescents with T1D, demonstrating improvements in HbA1c and CGM metrics, albeit most participants did not achieve optimal glycemic control. This highlights yet ongoing challenges in diabetes management, emphasizing the need for continued proactive efforts on the part of health care professionals, youth, and caregivers.

The Impact of a Low-Carbohydrate Diet on Micronutrient Intake and Status in Adolescents with Type 1 Diabetes.

OBJECTIVE: The aim of this study was to evaluate the macronutrient and micronutrient intake and status in youth with type 1 diabetes mellitus (T1DM) following the consumption of a low-carbohydrate diet (LCD). RESEARCH METHODS AND PROCEDURES: In a prospective intervention clinical trial, adolescents with T1DM using a continuous glucose monitoring device were enrolled. Following a cooking workshop, each participant received a personalized diet regime based on LCD (50-80 g carbohydrate/day). A Food Frequency Questionnaire was administered, and laboratory tests were taken before and 6 months following the intervention. Twenty participants were enrolled. RESULTS: The median age was 17 years (15; 19), and the median diabetes duration was 10 years (8; 12). During the six-months intervention, carbohydrate intake decreased from 266 g (204; 316) to 87 g (68; 95) (p = 0.004). Energy intake, the energy percent from ultra-processed food, and fiber intake decreased (p = 0.001, p = 0.024, and p < 0.0001, respectively). These changes were accompanied by declines in BMI z-score (p = 0.019) and waist-circumference percentile (p = 0.007). Improvement was observed in the median HbA1c from 8.1% (7.5; 9.4) to 7.7% (6.9; 8.2) (p = 0.021). Significant declines below the DRI were shown in median intake levels of iron, calcium, vitamin B1, and folate. CONCLUSIONS: The LCD lowered ultra-processed food consumption, BMI z-scores and the indices of central obesity. However, LCDs require close nutritional monitoring due to the possibility of nutrient deficiencies.

Hypothalamic-pituitary-gonadal function, pubertal development, and fertility outcomes in male and female medulloblastoma survivors: a single-center experience.

BACKGROUND: Endocrine deficiencies, including hypothalamic-pituitary-gonadal axis (HPGA) impairment, are common in survivors of childhood and adolescent medulloblastoma. Still, data regarding pubertal development and fecundity are limited, and few studies assessed HPGA function in males. We aimed to describe HPGA function in a large cohort of patients with medulloblastoma. METHODS: A retrospective study comprising all 62 medulloblastoma patients treated in our center between 1987 and 2021, who were at least 2 years from completion of therapy. HPGA function was assessed based on clinical data, biochemical markers, and questionnaires. RESULTS: Overall, 76% of female patients had clinical or biochemical evidence of HPGA dysfunction. Biochemical evidence of diminished ovarian reserve was seen in all prepubertal girls (n = 4). Among the males, 34% had clinical or biochemical evidence of gonadal dysfunction, 34% had normal function, and 29% were age-appropriately clinically and biochemically prepubertal. The difference between males and females was significant (P = .003). Cyclophosphamide-equivalent dose was significantly associated with HPGA function in females, but not in males. There was no association between HPGA dysfunction and other endocrine deficiencies, length of follow-up, weight status, and radiation treatment protocol. Two female and 2 male patients achieved successful pregnancies, resulting in 6 live births. CONCLUSIONS: HPGA dysfunction is common after treatment for childhood medulloblastoma. This is seen more in females, likely due to damage to the ovaries from spinal radiotherapy. Our findings may assist in counseling patients and their families regarding risk to future fertility and need for fertility preservation.

The Mediterranean Diet for Adolescents with Type 1 Diabetes: A Prospective Interventional Study.

The Mediterranean diet (MED) is highly recommended. Medical nutrition therapy is the cornerstone of diabetes treatment. The primary outcome was to evaluate the change in micronutrient intake of youth with type 1 diabetes before and after a 6-month MED intervention; we also assessed adherence and glycemic control. Twenty adolescents, median age 18 years (interquartile range: 15.5-21), median diabetes duration 9 years (7-14), using continuous glucose monitoring devices, received personalized diet regimes based on MED. At 6 months post-intervention, the caloric intake remained unchanged; however, the carbohydrate proportion was lower (p = 0.058), and the intakes of some monounsaturated fats increased (p = 0.049). Sodium intake exceeded the recommended daily allowance by 250% (p = 0.653), before and after the intervention. For blood glucose, the percent TIR (time-in-range, 70-180 mg/dL) improved from 52% (38-60) to 63% (47-71) (p = 0.047). The total insulin dose decreased marginally, from 0.76 u/kg (0.64-0.97) to 0.72 u/kg (0.61-0.89) (p = 0.067). BMI z-score and waist circumference did not change (p = 0.316 and p = 0.161, respectively). Diastolic blood pressure percentile decreased from 73% (68-88) to 69% (50-79) (p = 0.028), and LDL cholesterol from 114 mg/dL (105-134) to 104 mg/dL (96-124) (p = 0.059). The Israeli Mediterranean diet screener score increased, from 8 (7-11) to 13 points (12-14) (p < 0.001). The MED-based intervention in youth with type 1 diabetes is feasible and leads to improvement in monounsaturated fat intake, TIR, and diastolic blood pressure. Other parameters show no change (caloric intake, BMI, and HbA1c).

Short Stature and Distinct Growth Characteristics in Angelman Syndrome.

Objectives - Angelman syndrome (AS) is a rare, genetic, neurodevelopmental disorder characterized by severe impairments in speech, cognition and motor skills accompanied by unique behaviors, distinct facial features and high prevalence of epilepsy and sleep problems. Despite some reports of short stature among AS patients, this feature is not included in the clinical criteria defined in 2005. We investigated growth patterns among AS patients with respect to mutation type, growth periods, family history and endocrine abnormalities. Methods - Data was collected from patients' medical files in AS national clinic. Mutation subtypes were divided to deletion and non-deletion. Four growth periods were defined: preschool, childhood, peak-height velocity, and final-height. Results - The cohort included 88 individuals (46 males), with 54 (61.4%) carrying deletion subtype. A median of 3 observations per individual , produced 280 data points. Final-height-SDS was significantly lower compared to general population (-1.23±1.26, p<0.001), and in deletion group vs. non-deletion (-1.67±1.3 vs. -0.65±0.96, p=0.03). Final-height-SDS was significantly lower compared to height-SDS in preschool period (-1.32 vs -0.47, p=0.007). Patient's final-height-SDS was significantly lower than the parents' (∆final-height-SDS=0.94±0.99, p=0.002). IGF1-SDS was significantly decreased compared to general population (-0.55±1.61, p=0.04), with lower values among deletion group (-0.70±1.44, p=0.01) Conclusions - AS patients demonstrate specific growth pattern with deceleration during childhood and adolescence resulting in significantly decreased final height compared to normal population, and even lower among deletion subgroup, which could be attributed to reduced IGF1 levels. We propose adding short stature to the clinical criteria and developing adjusted growth curves for AS population.