Hormone Research in Paediatrics最新文献

Introduction: Automated insulin delivery (AID) systems offer superior glycaemic control compared to non-AID in children with type 1 diabetes, yet their performance during real-life challenges, such as summer camps with physical activity, remains underexplored. This study evaluated AID efficacy based on time range (70-180 mg/dL), comparing AID systems against sensor-augmented pump therapy (SAP) during a summer camp in children with type 1 diabetes.

Methods: Data were collected from a 14-day diabetes camp (July 2024) involving 26 children (mean + SD age 10 ± 1.3 years), using Medtronic MiniMed 780G (n = 13), mylife CamAPS FX (n = 7), or SAP (n = 6). Continuous glucose monitoring (CGM)-derived metrics for the two AID systems and SAP were compared by means of t tests or Mann-Whitney U tests (p ≤ 0.05).

Results: Both AID systems showed a similar time in range over the camp (primary endpoint, 75.5 ± 7.5% for MiniMed 780G vs. 71.1 ± 11.16% for CamAPS FX; p = 0.30). No significant differences were found for other glycaemic metrics or insulin dosage. Overnight, MiniMed 780G had less time below 54 mg/dL (0.0% [IQR: 0.0; 0.0%]) than CamAPS FX (0.4% [IQR: 0.0; 0.7%]; p = 0.024). SAP had significantly lower time in range than both AID systems (75.0% [IQR: 70.0; 81.0%] vs. 56.0% [IQR: 55.0; 66.0%]; p = 0.006). A positive correlation was found between coefficient of variation and the total number of steps (r = 0.39; p = 0.0459).

Conclusions: Despite the camp's challenges, both AID systems were safe and effective, meeting recommended CGM-derived treatment targets. Furthermore, AID systems showed superior glycaemic control compared to SAP.

Introduction: Neonatal diabetes mellitus (NDM) is a rare monogenic disorder, typically diagnosed within the first 6 months of life. While NDM is well recognized globally, data from India regarding its clinical characteristics, treatment strategies, and long-term outcomes are scarce. We describe the molecular characterization, clinical phenotype, and follow-up of children with NDM, managed at a tertiary care pediatric diabetes clinic in northern India over the last 2 decades.

Methods: Data from children diagnosed with NDM between January 2005 and December 2024 were retrospectively analyzed. Genetic testing was performed using standard protocols.

Results: Thirty-two patients (10 females) with NDM, median age at diagnosis 13.2 (range: 1.6-36.5) weeks, were identified. Twenty-four patients had diabetic ketoacidosis at diagnosis. Pathogenic genetic variants were confirmed in 25 children, including KCNJ11 (11/25), the INS gene (4/25), and EIF2AK3 (3/25). An empirical sulfonylurea trial was initiated in 22 infants with good response in 13 (12 with variants in the KCNJ11 or ABCC8 genes). HbA1c levels among this cohort were significantly better than other genetic variants (41 [38, 45] vs. 75 [52, 81] mmol/mol). At a median follow-up of 6.6 years, the mean HbA1c was 56.33 ± 18.55 mmol/mol with two deaths (both EIF2AK3 gene related).

Conclusions: This study highlights the genetic heterogeneity of NDM in the North Indian population and emphasizes the significance of early genetic testing for personalized management. Empirical sulfonylurea trials proved successful in specific cases, considering that genetic testing is delayed in resource-limited settings.

Introduction: Genetic analysis is essential for diagnosing, treating, and predicting complications in neonatal diabetes mellitus (NDM) but is unavailable in some regions. Sulfonylureas are effective for NDM caused by KCNJ11 or ABCC8 mutations, which are among the most common genetic causes; therefore, they are often given before genetic testing. Unfortunately, in certain ethnicities, this mutation rarely occurs. This report presents a case of NDM with a heterozygous INS gene missense mutation and positive pancreatic autoantibodies in a single individual.

Case presentation: A three-month-old boy, born to non-consanguineous parents, presented with diabetic ketoacidosis and bronchopneumonia. Initial management included intravenous insulin and antibiotics, followed by sulfonylurea and detemir insulin. The patient demonstrated a good response at 5 months of age, but by 11 months, glucose control deteriorated with increased HbA1c, positive pancreatic autoantibodies, and declining C-peptide levels over 10 months, necessitating a transition from sulfonylurea to basal - bolus insulin regimen. Genetic testing at age 4 years identified a heterozygous missense mutation in the INS gene (c.325T>C, p.Cys109Arg), confirming a diagnosis of permanent NDM.

Conclusion: In settings where genetic testing is limited, cautious sulfonylurea use based on clinical algorithms is recommended. Regular monitoring of sulfonylurea response, pancreatic autoantibodies, and β-cell function is essential to guide therapy adjustments.

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.