Journal of Pediatric Endocrinology & Metabolism最新文献

Objectives: We performed a meta-analysis to compare the effects of orlistat on body mass index and serum lipids in overweight and obese adolescents.

Methods: The meta-analysis was conducted to identify randomized controlled trials (RCTs) published up to 1 August 2024. PubMed, Embase, and Cochrane Library databases were searched. The outcome measures body mass index (BMI) and serum lipids, such as total cholesterol (TC), total triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). The review of publications was conducted in accordance with the guidelines set forth in the Cochrane Handbook and the Preferred Reporting Project for Systematic Review and Meta-Analysis (PRISMA).

Results: This study has been registered with INPLASY (number INPLASY202480052). A total of 696 patients were included in five randomized controlled trials. The orlistat group reduced BMI compared to placebo in the short term (MD=-0.73, 95 % CI: -1.44 to -0.02, p=0.04, I²=73 %) but appeared to have little effect in the long term (MD=-1.72, 95%CI: -3.55 to 0.12, p=0.07, I²=84 %). The exciting thing is that orlistat can significantly improve blood lipid levels in children, TC (MD=-8.11, 95 % CI: -10.88 to -5.33, p<0.05, I²=0 %), TG (MD=-3.22, 95 % CI: -5.58 to -0.86, p<0.05, I²=0 %), LDL (MD=-6.06, 95 % CI: -8.75 to -3.37, p<0.05, I²=0 %), and HDL (MD=0.87, 95 % CI: 0.13-1.61, p<0.05, I²=31 %).

Conclusions: Orlistat has been linked to alter lipid levels in obese or overweight children. However, the evidence regarding its efficacy in reducing BMI is inconclusive, with inconsistent findings across short and long-term studies. Further randomized controlled trials are necessary to ascertain its long-term impact on prognosis.

Objectives: Mutations in the AVPR2 gene are the most common cause of nephrogenic diabetes insipidus (NDI). In-frame deletions of the AVPR2 gene are a rare variant that results in NDI. We report a novel variant of the p.H138del in an NDI family with twin male patients and three female carriers of different clinical phenotypes.

Methods: The proband's blood genome was sequenced with a panel, and the variants were classified according to ACMG/AMP (2015) guidelines. X chromosome inactivation (XCI) was analyzed in the peripheral blood of his mother, grandmother, and maternal aunt, respectively. The haplotypes of the X chromosome were determined using their STR loci.

Results: A novel in-frame deletion in the AVPR2 gene was detected in monozygotic-twin boys, and his mother, grandmother, and maternal aunt were heterozygous carriers. The two boys showed typical NDI, and their mother and grandmother presented polydipsia, polydipsia, and polyuria, but the maternal aunt did not have similar symptoms. The blood XCI results of the mother, grandmother, and maternal aunt showed random inactivation (36.18 , 48.37, and 49.30 %, respectively). The X haplotype indicated that the variant of the mother and grandmother was on their activated X chromosomes(Xa), while the maternal aunt's variant was on her inactivated X chromosome(Xi).

Conclusions: In-frame deletion of the AVPR2 gene within its functional domain can significantly affect protein function, which is one of the vital causes of NDI. The clinical variability of female carriers of AVPR2 is associated with underlying environmental and epigenetic factors or complex recombination of the X chromosomes.

Objectives: Idiopathic central precocious puberty (iCPP) is the most common cause of precocious puberty in girls. However, research on the psychological outcomes of iCPP girls is limited. To evaluated the psychological characteristics in iCPP girls in comparison to prepubertal girls throughout the first diagnosis and six-month follow-up period.

Methods: Eighty-five girls, age 6-8 years, and their caregivers were enrolled to the prospective cohort study. Three Thai-standardized questionnaires were used as psychological assessment tools, including Children's Depression Inventory (CDI), Parent Screen for Child Anxiety Related Disorders (SCARED) and Parent-Strengths and Difficulties Questionnaire (SDQ).

Results: Forty-six iCPP and 39 prepuberty girls were enrolled at baseline. No significant differences in psychological and behavioral problems between iCPP and prepuberty girls. However, the iCPP group exhibited a significantly higher proportion of "risk and problem" for emotional problems compares to the prepuberty group (7 vs. 0, p=0.01) while the prepuberty group exhibits the significantly proportion of "risk" for peer problems (6 vs. 0, p=0.007). At baseline, twelve percent of iCPP girls exhibited depression and mean CDI score was 8.1 ± 7.2 and 3.7 ± 2.3 (p=0.007) in iCPP and prepuberty group, respectively. At the 6-month follow-up, there was no significant difference in psychological outcomes between two groups.

Conclusions: There were no significant differences in psychological and behavioral problems in iCPP girls compared to prepubertal girls. However, the higher prevalence of emotional problems and depression observed in iCPP girls constitutes significant psychological issues that necessitate close monitoring.

Objectives: We describe a male with adrenal hypoplasia congenita (AHC) caused by a novel mutation in NR0B1, who was noted at 9 months of age to have central precocious puberty (CPP).

Case presentation: A 3-week-old full-term male presented with hypothermia and lethargy, and a 0.3 kg weight loss since birth. Labs were consistent with adrenal crisis, he was stabilized with stress dose hydrocortisone (HC), insulin, and antibiotics, and he was admitted to the Pediatric Intensive Care Unit. Subsequent labs revealed primary adrenal insufficiency with abdominal ultrasound remarkable for nonvisualization of the adrenal glands. Genetic testing identified a novel pathogenic c.707G>A [p.Trp236ter] nonsense variant in the DNA-binding domain of NR0B1 (DAX-1) confirming AHC. The patient was discharged with HC, fludrocortisone, and sodium supplementation with good tolerance and interval weight gain and normal electrolytes. At 9 months of age, the patient developed signs of precocious puberty, which failed to self-resolve or diminish with increased dosing of HC, and by the age of 15 months, he was treated with leuprolide acetate.

Conclusions: Historically, hypogonadotropic hypogonadism has been observed in 76 % of adolescent patients with AHC who have alterations in NR0B1. CPP has been infrequently described in AHC, and the natural history and management of CPP in this setting is not established. Our observations may contribute to the understanding of factors influencing normal and abnormal puberty in infants. Increased awareness of the possibility of CPP in AHC will aid clinicians in the earlier clinical and laboratory detection of this complication.

Objectives: Steroid 5α-reductase type 2 deficiency (5α-RD2) is an autosomal recessive disorder caused by mutations in the SRD5A2 gene. This condition is characterized by reduced enzymatic activity of the 5α-reductase type 2 enzyme. Individuals with mutations in the SRD5A2 gene may exhibit various symptoms of under-masculinization in 46, XY individuals. We conducted a comprehensive analysis of the SRD5A2 gene in a patient with disorder of sex development (DSD).

Case presentation: We describe a patient with a homozygous Gly183Ser variant in the SRD5A2 gene. Their sibling also carries this variant in homozygosity, while both parents have it in a heterozygous state. The patient presents with predominantly female traits and was raised as a girl. Although the siblings exhibit distinct phenotypic characteristics, both have assumed a male gender identity.

Conclusions: This study reveals different phenotypes for the two siblings, highlighting the complexity of establishing a genotype-phenotype correlation in the SRD5A2 gene. It is noteworthy that the Gly183Ser variant seems to be more prevalent among individuals of African descent, aligning with our patient's ethnic background.

Objectives: The study endeavored to evaluate the prolonged efficacy and safety of PEGylated rhGH (PEG-rhGH) administration in Chinese children diagnosed with growth hormone deficiency (GHD) over a 5-year period.

Methods: A retrospective analysis was conducted on children with GHD, who received a 0.2 mg/kg/week dose of PEG-rhGH between 2016 and 2023 in our department.

Results: The height standard deviation score (Ht SDS) exhibited a marked elevation post-PEG-rhGH administration (p<0.001), sustaining this enhancement beyond year 3, with increments recorded at 0.94±0.37, 1.49±0.48, 1.77±0.51, 2.12±0.65, and 2.15±0.58 across 5 years. Similarly, the height velocity (HV), insulin-like growth factor-1 standard deviation score (IGF-1 SDS), and bone age to chronological age ratio (BA/CA ratio) underwent significant augmentations (p<0.01). Remarkably, no signs of rapid bone maturation were detected during the 5-year observation. Among the participants, 31 patients (59.62 %) experienced adverse events, of which eight instances (15.38 %) were classified as treatment-related adverse events, but none were severe or unexpected. Additionally, high-density lipoprotein (HDL) levels rose while low-density lipoprotein (LDL) levels fell, both remaining within the standard range throughout the treatment phase.

Conclusions: Administering PEG-rhGH at a dosage of 0.2 mg/kg/week proved both effective and well-tolerated in treating prepubertal children with GHD. This regimen also demonstrated positive impacts on lipid metabolism over an extended treatment period.

Objectives: To study the urinary neutrophil gelatinase-associated lipocalin (NGAL) and beta-2-microglobulin (β2M) levels as markers of tubular damage in children with type 1 diabetes (T1DM).

Methods: Forty T1DM children and 40 age-matched controls were enrolled. Subjects with coexisting kidney disorder, intake of oral glucose lowering drugs and syndromic diabetes mellitus were excluded. Fasting plasma glucose, glycated hemoglobin (HbA_1c), kidney function, urinary albumin-creatinine ratio (UACR), NGAL and β2M were measured and compared in cases and controls.

Results: The median (IQR) age of cases and controls was 10.6 (8, 14.2) and 10.7 (8.4, 13.7) years, respectively. Cases had disease duration of 4 (3, 6.8) years and HbA_1c 10.9 (9, 13.1) %. Microalbuminuria was seen in 14 (35 %). Median (IQR) levels of UACR were higher in cases than controls [19.38 (10.27, 35.26) and 6.49 (3.10, 11.65) µg/mg; p<0.001], similarly NGAL/creatinine [352.21 (191.49, 572.45) and 190.54 (125.91, 322.83) ng/mg; p=0.006], unlike β2M/creatinine [1.7 (0.43, 6.02) and 2.12 (1.05, 4.47) µg/mg; p=0.637]. Children with higher HbA_1c (≥10 %) had higher urinary ACR and tubular biomarkers than HbA_1c<10 % (p>0.05). Urinary ACR showed positive correlation with NGAL/creatinine (r=0.38, p=0.019) and β2M/creatinine (r=0.42, p=0.009).

Conclusions: Urinary biomarkers NGAL and β2M were elevated in the presence of normal urinary microalbumin levels suggestive of early tubular damage in T1DM.

Objectives: We are reporting a rare case series of 2 siblings and their mother with diabetes having a CFAP126 gene mutation.

Case presentation: Two female siblings, presented with incidental hyperglycemia at the ages of 16 and 13. They had a strong family history of diabetes on the maternal side. The systemic examination was unremarkable. Sibling 1 had HbA1C of 12.3 % with insulin and C-peptide levels of 6.6 IU/L and 1.8 ng/mL, respectively. Sibling 2 had an HbA1C of 12.6 %, an insulin level of 7.3 IU/L, and a C-peptide level of 2.02 ng/mL. Anti-GAD-65 and IA2 antibodies were negative. Mother also shared similar clinical processes and exhibited comparable biochemical changes related to glucose metabolism with elevated HbA1C levels and negative autoimmune markers (anti-GAD65 and IA2 antibodies). Whole exome sequencing (WES) turned out to be negative for MODY variants but revealed a rare heterozygous mutation in the CFAP126 gene (c.310A>T p. (Lys104*) in this family including both siblings and mother. The pathogenicity prediction tool MutationTaster^® classified the mutation as disease causing. Oral glibenclamide remarkably reduced insulin requirements and improved HbA1C levels.

Conclusions: This rare genetic mutation is likely associated with diabetes and possibly a novel marker for a yet to be identified type of diabetes, that is responsive to oral sulfonylureas. The influence of this gene on insulin secretion needs to be confirmed through future research.

Objectives: To generate normative data and validate the recently developed, gender-neutral, External Genitalia Score (EGS) in Indian preterm and term neonates and children up to 2 years of age with normal and atypical genitalia.

Methods: This observational study included 1,040 neonates born between 28 and 42 weeks of gestation and 152 children between 1 and 24 months of age. In addition, 50 children with disorders of sex development (DSD) were also enrolled in the study. The Prader stage/external masculinization score (EMS) (as applicable), anogenital ratio (AGR) and EGS were assessed for all neonates and children with typical and atypical genitalia.

Results: Median EGS values in newborn males with typical genitalia were 9.5 at 28-31 weeks, 10.5 at 32-33 weeks, 11 at 34 weeks and 11.5 in males at 35-42 weeks of gestation. For all females with typical genitalia, the EGS was 0. EMS and EGS showed a positive correlation in males with typical genitalia (r=0.421, p=0.000**) and all children with DSD (r=0.857, p=0.000**). Mean AGR in males and females with typical genitalia and those with DSD were 0.52±0.07, 0.31±0.05 and 0.47±0.13, respectively. EGS correlated with AGR in all males with typical genitalia (r=0.107, p=0.008**), and in all children with DSD (r=0.473, p=0.001**).

Conclusions: The EGS enables accurate, gender-neutral and comprehensive assessment of external genitalia in Indian neonates and children with typical and atypical genitalia/DSD. Evaluation for DSD is recommended in any child with EGS greater than 0 and ≤10th percentile for gestation or age (10.5 in a term neonate).