Hormone Research in Paediatrics最新文献

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Background: Childhood obesity has become a global pandemic and is one of the strongest risk factors for cardiovascular disease later in life. The correlation of epigenetic marks with obesity and related traits is being elucidated. This review summarizes the latest research and its challenges in the study of epigenetics of (childhood) obesity.

Summary: Epigenome-wide association studies helped to identify novel targets and methylation sites that are important in the pathophysiology of obesity. In the future, such sites will become essential for developing methylation risk scores (MRS) for metabolic and cardiovascular diseases. Although MRS are very promising for predicting the individual risk for obesity, the implementation of MRS is challenging and has not been introduced into clinical practice so far.

Key messages: Future research will undoubtedly discover numerous methylation sites that may be involved in the development of obesity and its comorbidities, especially at a young age. This will contribute to a better understanding of the complex etiology of human obesity. From a clinical perspective, the overarching aim is to generate MRS that are robust for reliable and accurate prediction of obesity and its comorbidities.

Introduction: Pseudohypoparathyroidism 1A (PHP1A) is the best-known representative of inactivating PTH/PTHrP signaling disorders (iPPSD). The associated phenotype develops over time and often includes hormonal resistances, short stature and osteoma cutis. More complex and very early manifestations have also been reported. Neonatal complications may indicate a more severe course of the disease. Here we report 3 patients with heterozygous GNAS-variants and infancy-onset of iPPSD2 / PHP1A.

Case presentations: Patient 1 is a 15-month-old boy, who presented with severe chronic noninfectious diarrhea and elevated TSH beginning at 1 month of age, leading to life-threatening failure to thrive. Patient 2 is a 4-year-old boy with a history of bronchopulmonary dysplasia as well as neonatal-onset severe pulmonary complications, including critical pulmonary bleeding and recurring pulmonary infections and TSH elevation. Patient 3 is a 4-year-old girl, who exhibited signs of PTH resistance and progressive osteoma cutis at the age of 1-2 weeks and obesity at the age of 3 months.

Conclusion: The phenotypic spectrum of iPPSD2/ PHP1A in neonates and infants may include severe gastrointestinal, pulmonary and endocrine manifestations, which may delay diagnosis if not recognized as a spectrum-disorder of Gsα deficiency. The cases support the hypothesis that early-life manifestations may indicate a more complicated course of the disease. Elevated PTH or TSH in infants with unclear symptoms or conditions should prompt evaluation for disorders of the iPPSD spectrum. In the absence of reliable predictors for the individual courses of PHP1A, in depth clinical screening for possible manifestations beyond the classical spectrum is warranted even in infancy.

Introduction: This is a report of a child with congenital hyperinsulinism associated with a loss-of-function variant in KCNE1. KCNE1 encodes a human potassium channel accessory (beta) subunit that modulates potassium channel Kv7.1 (encoded by KCNQ1). Loss-of-function pathogenic variants in either the KCNQ1 or KCNE1 genes result in long QT syndrome by causing prolongation in the action potential duration at the cellular level. In addition to long QT syndrome, the phenotype associated with loss-of-function pathogenic variants in KCNQ1 is characterized by postprandial hyperinsulinemic hypoglycemia.

Case presentation: Clinical data for the proband were extracted from the medical records. The proband presented with fasting hypoglycemia due to hyperinsulinism in early childhood as well as postprandial hypoglycemia triggered by carbohydrates and by protein. Whole-exome sequencing was undertaken in genomic DNA isolated from proband and both parents. Whole-exome sequencing revealed a variant in KCNE1 inherited from the father, who also has a history of hyperinsulinism. Both the patient and father were subsequently diagnosed with long QT syndrome. The proband and father underwent phenotype testing including fasting test, oral glucose tolerance test, oral protein tolerance test, and exercise tolerance test.

Conclusions: This case illustrates that loss-of-function variants in KCNE1, similar to KCNQ1, are associated with a cardiac and a beta cell phenotype, and thus, this patient population should be screened for hypoglycemia, particularly in the postprandial state.

Introduction: Some adolescents undergoing metabolic and bariatric surgery (MBS) have suboptimal responses to surgery, particularly over the longer term. This study aimed to quantify changes in weight loss over time in adolescents undergoing MBS and identify preoperative predictors of weight loss.

Methods: This was a prospective, observational cohort study of 73 adolescents (12-19 years) living with obesity undergoing MBS. Absolute and relative changes in anthropometric and biochemical parameters were evaluated up to 30 months. Changes in anthropometric measures were assessed using a mixed residual maximal likelihood model. Univariable and multivariable logistic regression were used to identify predictors of a >35.0% reduction in BMI z-score from baseline to 12 months. Predictive accuracy was assessed by area under the receiver operating characteristics analysis.

Results: Most patients (87.7%) underwent laparoscopic sleeve gastrectomy (12.3% underwent laparoscopic sleeve bypass). Weight, weight z-score, BMI, and BMI z-score significantly decreased over 30 months (p < 0.001) up to a -53.8% relative change in BMI z-score at 30 months. There was a significant increase (p = 0.02) in high-density lipoprotein cholesterol and a significant decrease in triglycerides (p = 0.0001) and ALT (p = 0.0004) after surgery. A higher preoperative BMI was associated with a reduced odds (OR 0.89, 95% CI 0.79-0.97, p = 0.03) of a >35% reduction in BMI z-score at 12 months. A baseline BMI >52.6 kg/m2 had a sensitivity of 100% and specificity of 40.6% for detecting a >35.0% postoperative decrease in BMI z-score.

Conclusion: MBS results in sustained weight loss in adolescents. A high preoperative BMI predicts resistance to optimal weight loss after surgery and argues against delaying surgery once eligibility thresholds are met.

Introduction: Thyrotoxic hypokalemic periodic paralysis (THPP) is a rare but severe complication of hyperthyroidism characterized by acute muscle weakness. This study reports the first case of THPP in an adolescent with type 1 diabetes mellitus (T1DM) and Graves' disease, triggered by high-dose insulin, high carbohydrate intake, and strenuous exercise. It highlights the clinical presentation, management, and implications of THPP in this context.

Case presentation: A 17-year-old male patient with T1DM and Graves' disease presented to the emergency department with weakness in the extremities. The patient had engaged in strenuous exercise and high-dose rapid-acting insulin, and consumed a large amount of rice shortly before the onset of the symptoms. He exhibited hypertension and tachycardia, with diminished muscle strength and deep tendon reflexes with severe hypokalemia (1.6 mmol/L). Treatment with potassium and magnesium replacements was initiated. The patient's symptoms resolved within 5 h, and his neurological examination was normalized. Hypokalemia did not recur during follow-up. All symptoms improved rapidly with potassium replacement, β-blocker therapy, and antithyroid treatment.

Conclusion: This case represents the first documented instance of THPP in an adolescent with T1DM and Graves' disease. This entity should be included in the differential diagnosis of acute paralysis in patients with known thyrotoxicosis or those exhibiting symptoms such as tachycardia and hypertension. Insulin treatment in a hyperthyroid diabetic patient may increase the risk of THPP.

Introduction: Most of the loss-of-function mutations described in children with central precocious puberty (CPP) are located in the coding regions of MKRN3 or DLK1 genes. Notably, potential abnormalities in the regulatory regions of these CPP genes are rarely explored. The objective of this work was to identify pathogenic allelic variants in the regulatory regions of MKRN3 and DLK1 genes in patients with familial or idiopathic CPP.

Methods: A cohort of 217 individuals with CPP (205 girls and 12 boys; 143 sporadic cases and 74 familial cases) was investigated. Rare and potentially pathogenic variants in the coding regions of both genes were previously excluded. Analyses of the regulatory regions of MKRN3 and DLK1 were performed using polymerase chain reaction and direct automated sequencing (Sanger method). Circulating serum levels of MKRN3 and DLK1 proteins were measured using an ELISA assay.

Results: We identified a heterozygous allelic variant (c.-265G>A), previously associated with CPP, located in the promoter region of the MKRN3 gene in three girls from two unrelated families. In silico prediction analysis indicated that the c.-265G>A variant was in the ZNF384 binding region. ZNF384 gene encodes a C2H2-type zinc finger protein, which might act as a transcription factor. MKRN3 serum levels varied from 197.5 pg/mL to 1,907 pg/mL and were relatively lower in patients with CPP who carried the c.-265G>A variant. No pathogenic allelic variant was found in the regulatory region of the DLK1 gene.

Conclusion: Pathogenic variants in the regulatory region of MKRN3 gene are rare and can be associated with the CPP phenotype.

The International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines represent a rich repository that serves as the only comprehensive set of clinical recommendations for children, adolescents, and young adults living with diabetes worldwide. This chapter builds on the 2022 ISPAD guidelines, and updates recommendations on the glycemic targets for children and adolescents living with diabetes. A new target for hemoglobin A1c (HbA1c) of ≤6.5% (48 mmol/mol) is recommended for those who have access to advanced diabetes technologies like continuous glucose monitoring and automated insulin delivery. This target should be encouraged for all children and adolescents living with diabetes when safely achievable. In other settings, the HbA1c target is ≤7.0% (53 mmol/mol).