Hormone Research in Paediatrics最新文献

Introduction: Children born with lower birth weight face an increased risk of developing cardiovascular disease later in life. We hypothesize that cardiovascular protein biomarkers in cord blood, associated with birth weight SDS and systolic cardiac function, may reveal mechanisms behind early programming of cardiovascular function.

Methods: We investigated the association between birth weight SDS and plasma levels of 184 circulating proteins determined by Proximity Extension Assay (PEA) in cord blood from 48 children. The birth weight-associated proteins were correlated with left ventricular longitudinal strain (LVLS) determined by echocardiography at birth and 3 months of age.

Results: We identified seven cardiovascular protein biomarkers associated with birth weight SDS: stem cell factor, leptin, elafin, insulin-like growth factor-binding protein-1, follastatin, paraoxonase, and epithelial cell adhesion molecule (Ep-CAM). Among these, Ep-CAM significantly correlated with LVLS at 3 months of age.

Conclusion: PEA successfully identified both established and novel proteins associated with fetal growth and birth size, including one novel protein related to LVLS. This indicates that our approach is promising for uncovering biological pathways that may be involved in direct programming of cardiovascular function in children and affect the risk of cardiovascular disease in adulthood.

Introduction: PHAI encompasses two distinct forms of aldosterone resistance, with unique clinical and endocrine manifestations and genetic patterns, autosomal dominant (AD) and autosomal recessive. The AD form is caused by heterozygous mutations on the NR3C2 gene on chromosome 4q31, coding for the aldosterone receptor. The salt-wasting symptoms usually present in early infancy. The patients require intravenous/oral sodium chloride therapy until the age of 1-3 years. In the absence of family history, the diagnosis is delayed in many infants for even months. The importance of prenatal diagnosis in pregnancies with other affected family members has not been evaluated. We hereby report the effect of prenatal molecular diagnosis and immediate oral salt therapy on the postnatal disease course.

Case report: The patient was born at 39 weeks. Pregnancy and delivery were uneventful. The birth weight was 3,038 g. Family history was significant for a large heterozygous deletion encompassing exons 4 to 9 of the NR3C2 gene in her mother and brother. They were symptomatic at birth. We evaluated the MR gene analysis in the fetus by amniocentesis, which showed the same mutation found in the mother. Oral salt therapy was started on day 1. The growth parameters and sodium concentrations remained normal for 8 months with normal to borderline high potassium.

Conclusion: Prenatal genetic diagnosis and prompt salt supplementation after birth prevent the clinical manifestations resulting from salt wasting.

Introduction: Hypomagnesemia type 1 (HOMG1) is a rare autosomal recessive condition due to TRPM6 gene mutation, leading to primarily impaired intestinal magnesium absorption resulting in secondary hypocalcemia. This study aimed to determine the clinical spectrum of hypomagnesemia with secondary hypocalcemia due to TRPM6 mutation.

Methods: Retrospective study carried out for a period of 2 years at the Department of Pediatric Endocrinology and Diabetes, University of Child Health Sciences, The Children's Hospital, Lahore. All genetically confirmed cases of primary hypomagnesemia due to TRPM6 mutation were clinically and biochemically reviewed to look at their clinical spectrum.

Results: Eleven patients (n = 7 male) with homozygous TRPM6 mutation (7 novel variants) from ten different families were reported. Six cases (5 families) had a history of sibling death due to hypocalcemia seizures. Irritability and excessive crying were the first symptoms (mean age = 20 days) followed by intractable seizures (mean age = 2.07 months) in our cohort. Eight patients presented to tertiary care hospital under 6 months of age, 2 between 6 and 12 months, and 1 at 3 years of age. Initial biochemical profile in all cases revealed low magnesium, low calcium, normal/high phosphate, normal alkaline phosphatase, low/normal parathyroid hormone, normal/high 25-OH D level, and low fractional excretion of Mg. All were started on daily oral magnesium with the aim of achieving a normal biochemical profile including magnesium level. All cases are currently maintaining their bone profile on oral magnesium and are seizure free.

Conclusion: HOMG1 due to TRPM6 mutation is a rare condition. We are reporting 11 cases of TRPM6 mutation due to 9 different variants (7 novel). Persistent severe secondary hypocalcemia is a prominent clinical feature of TRPM6 mutation, which can be life-threatening if not treated promptly.

Introduction: Multidisciplinary care can improve glycemic outcomes in individuals with type 1 diabetes (T1D). Yet, prior studies suggest limited utilization of team-based care and either no reimbursement or inadequate reimbursement for diabetes and nutritional education, mental health, and social support as well as remote services. We sought to evaluate multidisciplinary care services offered by pediatric diabetes centers to understand whether current practices are sustainable.

Methods: The Pediatric Endocrine Society Diabetes Special Interest Group collaborated with the T1DX-Quality Improvement Collaborative to survey US pediatric diabetes centers on care delivery practices and resources for new onset and ongoing care, introduction of technology, and telehealth focusing on team-based approaches.

Results: We analyzed responses from 31 centers, mostly academic, from 16 states and Washington DC representing all geographical regions providing care for 45,759 youth with T1D who had at least one visit in 2022. Most centers (74%) provided initial diabetes education in the inpatient setting using clinic-employed staff. The majority initiated CGMs at or close to diagnosis and offered insulin pump therapy within the first year. All but one center encouraged communication with diabetes teams between visits. Less than half of practices estimated that at least 50% of their youth with T1D received mental health services and assessments for social concerns annually. Telehealth was utilized by all centers. Many centers indicated suboptimal reimbursement, and 87% operated at a budget deficit.

Conclusion: Despite the commitment of pediatric diabetes centers to provide high-quality multidisciplinary care, many youth with T1D may not receive the services as frequently as recommended. These services are often unreimbursed. We advocate for alternative reimbursement models for clinical workflows that support the delivery of individualized, multidisciplinary care aligned with best practices shown to improve clinical outcomes and quality of life for youth with T1D. Examples include expansion of telemedicine and remote monitoring, non-face-to-face acute and routine care, navigation of technology, supplies and services, engagement and coordination of community-based resources among others. Such models would promote equitable, needs-based care while enabling centers to operate efficiently.

Background: It is not known whether the extent of pubertal development influences the treatment effects in very young transgender people undergoing puberty suppression (PS) and gender-affirming hormone therapy (GAHT). This study aimed to investigate how anthropometric parameters and body composition change according to birth-assigned sex and affirmed gender during PS and GAHT.

Methods: This retrospective study included data from 201 adolescents starting PS under 15yr at a national gender service (139 trans boys and 62 trans girls). Data from 127 of them who subsequently received GAHT were available. Height, weight, BMI, total lean, fat and muscle mass (LM, FM and MM) were collected using Tanita body composition analyzer.

Results: 'In puberty' trans boys (Tanner stage 2-3), total FM increased on PS (2.49 kg, 95% CI 1.66;3.33) similarly to LM (2.41 kg, 95% CI 1.85;2.97), while in 'completing puberty' trans boys (Tanner stage 4-5) the increase of total FM (1.80 kg, 95% CI 1.21;2.39) was higher than total LM (0.97 kg, 95% CI 0.63;1.30). 'In puberty' trans boys showed increasing mean FM z-scores from baseline after 3 years of PS (from 0.70 to 1.2). Mean LM z-scores decreased in both 'in puberty' (from 0.98 to 0.5) and 'completing puberty' (from 1.16 to 0.80) trans boys. During GAHT, 'in puberty' trans boys showed a greater increase of total LM and MM (respectively 6.28 kg, 95% CI 3.54;9.02 and 6.08 kg, 95% CI 3.64;8.51). Both groups 'in puberty' and 'completing puberty' trans boys did not show a further increase in total FM. In contrast, 'completing puberty' trans girls showed the greatest increase of total FM during PS (4.27 kg, 95% CI 1.50;7.03). MM and LM % decreased throughout PS in all trans girls, whereas body composition only changed slightly during GAHT.

Conclusions: The effect of PS on body composition is more pronounced in 'in puberty' trans adolescents, and 'in puberty' trans boys are more responsive to GAHT, showing greater increases in MM and LM. In trans girls, the most significant increase in FM, along with reduction in LM and MM, occurs during PS, whereas no substantial changes were observed during subsequent GAHT. This suggests that any effect on physical performance may depend on pubertal development at the start of intervention.

Background: Despite guidelines emphasizing the importance of a structured pediatric-to-adult healthcare transition (HCT) for individuals with congenital adrenal hyperplasia (CAH), significant gaps remain in understanding the transition experiences and long-term outcomes of this population. This scoping review examines existing research on HCT for emerging adults with CAH.

Summary: PubMed, Scopus, and Embase databases were systematically searched to identify research exploring the HCT of individuals with CAH. Eighteen studies met the inclusion criteria. Findings were categorized as: (1) HCT readiness and communication, (2) HCT programs and outcomes, and (3) HCT experiences and considerations. Barriers hindering effective HCT include clinician shortages, distance to specialty care centers, and socioeconomic challenges. Knowledge gaps include patient and parent perspectives, a lack of validated transition readiness measures, insufficient long-term health outcome data, intervention research, and data on self-management skills. Addressing these gaps is essential to enhancing patient outcomes and continuity of care.

Key messages: This review highlights the importance of strategies, including effective communication, structured HCT programs, and transition readiness measures, to improve outcomes for individuals with CAH. Challenges, such as inconsistent metrics, logistical barriers, and high rates of care dropout, demonstrate the need for further research, tailored interventions, and advocacy to optimize HCT practices.

Introduction: Recent research has expanded the spectrum of genetic causes for growth failures. Patients with CUL3-related neurodevelopmental disorder (NDD) present with variable phenotypic manifestations, and growth retardation has been observed in some of these patients.

Case presentation: We present two families with NDD and variable degree of short stature. The proband in Family 1 had short stature (-3.0 SDS), developmental delay, learning difficulties, and autism spectrum disorder. Whole exome sequencing (WES) revealed a novel likely pathogenic heterozygous nonsense CUL3 variant c.420C>G, p.Tyr140Ter. The variant was also identified in her non-identical twin sister, who presented with short stature and NDD, and in their father, who had NDD and epilepsy but normal height. The proband and her sister were treated with growth hormone (GH) with good response. The proband and his brother in Family 2 presented with short stature during childhood, NDD, and facial dysmorphism. WES identified a heterozygous likely pathogenic nonsense CUL3 variant c.442C>T, p.Arg148Ter in the proband and his brother. The variant was inherited from their mother, who had facial dysmorphism and hypertension but normal height.

Conclusion: CUL3-related NDD can be associated with growth retardation. We observed a good response to GH therapy in 2 of our patients with short stature. Our finding expands the spectrum of disease-causing variants in CUL3 and demonstrates variable intra-familial clinical expressivity.

Introduction: Acquired generalized lipodystrophy (AGL) is a rare condition characterized by body fat loss and, usually, metabolic syndrome with or without associated autoimmune diseases. Clinical phenotypes of AGL are heterogenous, making diagnosis and management challenging. Here, we present a case of AGL with a unique and dominant autoimmune phenotype that prompts discussion of this rare disorder, the prolonged clinical course, and its optimal management.

Case presentations: A two and a half-year-old girl presented with thinning of her arms and legs and vitiligo. She subsequently developed alopecia at age four and Graves' disease at age twelve with associated Graves' eye disease. By age fourteen, she developed Addison's disease and typical features of severe AGL with fat loss from the extremities and buttocks, venomegaly, muscle hypertrophy, and acanthosis nigricans. She had mild dyslipidemia but normal fasting insulin, HbA1c, and leptin levels. Although her parents were consanguineous, next-generation sequencing of a targeted but comprehensive lipodystrophy gene panel was negative. The negative genetics, clinical features, and presence of autoimmune diseases favored a diagnosis of AGL.

Conclusion: This case is unusual in that (i) it was associated with several autoimmune diseases (Graves' disease, Addison's disease, vitiligo, and alopecia); (ii) leptin levels were normal despite lipodystrophy; (iii) her Graves' disease was associated with severe eye disease. Given the distinct but unusual phenotype (multiple autoimmune diseases associated with generalized lipodystrophy in the absence of hypoleptinemia) and parental consanguinity, despite negative targeted gene sequencing, our patient's AGL may have been due to a novel, autosomal recessive genetic variant. Whole-genome sequencing would be useful in this case to try to determine a genetic cause to provide new insights into AGL and the underlying autoimmune mechanisms.