Journal of Pediatric Endocrinology & Metabolism最新文献

Objectives: The aim of the current study was to assess the natural course of partial remission (PR) phase of type 1 diabetes (T1D) and to highlight the putative association between vitamin D receptor (VDR) (Fok1) gene polymorphism and PR phase.

Methods: Ninety participants with newly diagnosed T1D were followed up for a total of 12 months. The VDR (Fok1) rs2228570 gene polymorphism was genotyped using allelic discrimination (AD) assay.

Results: Fifty-four patients (60 %) reached PR with an average duration of 5.63 ± 2.9 months. Among remitters, the frequency of CC "FF" genotype and allelic frequency of C "F" were significantly higher (p<0.001). Furthermore, participants expressing "CC" genotype had earlier onset of PR and spent a significantly longer duration in remission (p<0.001). Younger age (p<0.001; OR 41.6; CI 12.12-142.99), absence of DKA (p<0.001; OR 16, CI 4.36-50.74), higher C-peptide levels (p<0.001; OR 19.55; CI 6.52-58.63), and presence of CC "FF" genotype of VDR (p<0.001; OR 6.74; CI 2.41-18.86) best predicted the overall occurrence of PR.

Conclusions: Younger age, less extent of metabolic derangements, and expression of a CC "FF" genotype were found to influence the occurrence of PR. Data from the current study showed that the "C" allele could have a protective role on preserving residual β-cell mass and could predict both onset and duration of PR among newly diagnosed T1D. These findings support the growing concept of future tailored precision medicine.

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: 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).

Objectives: Lipoid congenital adrenal hyperplasia (LCAH) is a rare autosomal recessive disease caused by mutations in the steroidogenic acute regulatory protein (STAR) gene, expressed in the adrenal and gonadal tissues. In classical LCAH, individuals with 46, XY chromosomes present with a female appearance of the external genitalia due to insufficient androgen production. In the non-classical form, a milder phenotype is observed with male external genitalia. Here, we present a non-classical LCAH diagnosis with a newly identified c.266T>A (p.Ile89Asn) likely pathogenic homozygous variant in a 46, XY infant.

Case presentation: A three-month-and-thirteen-day-old male proband presented with clinical features of cortisol and mineralocorticoid deficiencies. The manifestation of salt-wasting syndrome occurred relatively late, and although the external genitalia appeared male, there was a mild virilization defect. The combination of mild impairment in androgen production and severe salt-wasting syndrome is an intriguing finding in our patient. Peripheral blood samples were obtained from the patient and his family. The newly identified variant, determined by next-generation sequencing analysis, was confirmed by segregation analysis showing carrier status in both parents.

Conclusions: We aim to contribute to the literature by elucidating molecular mechanisms by presenting an atypical presentation and a newly identified variant.

Objectives: This study aims to investigate the clinical features of differentiated thyroid carcinoma (DTC) in children and adolescents under 18 years and assess the impact of surgery combined with thyroid hormone and radioactive iodine (RAI) on their prognosis.

Methods: A retrospective observational study was conducted, involving children/adolescents with DTC who underwent surgery at the Head and Neck Department of Tianjin Medical University Cancer Institute and Hospital from January 1998 to December 2018.

Results: Among 198 patients, 130 (65.7 %) were female. According to the American Thyroid Association guidelines, cases were categorized as low (106, 53.5 %), intermediate (54, 27.3 %), and high (38, 19.2 %) risk. The follow-up duration ranged from 3 to 23 years. Local recurrence and distant metastasis were identified in 21 (10.6 %) and 14 (7.1 %) cases, respectively. All patients received levothyroxine, while RAI therapy was administered to intermediate- and high-risk patients. The local recurrence and distant metastasis rates in these two groups were 33.3 and 39.5 %, respectively, with no recurrence or metastasis in the low-risk group. Persistent without structural evidence of disease were 0.9, 3.7, and 26.3 % at end of follow-up for the low-, intermediate-, and high-risk groups, respectively. The overall survival rates for all three groups were 100 %, while disease-free survival rates were 99.1, 63.0, and 34.2 % for the low-, intermediate-, and high-risk groups, respectively.

Conclusions: Children/adolescents with low-risk DTC exhibited a favorable prognosis even without RAI. However, intermediate- and high-risk DTC patients, despite RAI and levothyroxine treatment, showed elevated rates of persistent disease, local recurrence, and distant metastasis.

Objectives: Pseudohypoparathyroidism (PHP) comprises a cluster of heterogeneous diseases characterized by hypocalcemia and hyperphosphatemia due to parathyroid hormone (PTH) resistance. PHP type 1B (PHP1B) is caused by heterozygous maternal deletions within GNAS or STX16. STX16 exon 2-6 deletion is commonly observed in autosomal dominant (AD)-PHP1B, while sporadic PHP1B commonly results from methylation abnormalities of maternal differentially methylated regions and remains unclear at the molecular level.

Case presentation: A 39-year-old male patient with PHP1B, who had his first seizure at 15 years of age, presented to our hospital. The methylation-specific multiplex ligation-dependent probe amplification results showed a half-reduced copy number of STX16 exon 5-7 and loss of methylation at GNAS exon A/B. His mother also had a half-reduced copy number of STX16 exon 5-7 but with normal methylation of GNAS. His father has a normal copy number of STX16 and normal methylation of GNAS.

Conclusions: For the recognition and early diagnosis of this kind of disease, here we report the clinical symptoms, auxiliary examinations, genetic testing characteristics, and treatment of the patient.

Objectives: Pseudohypoaldosteronism type 1 (PHA1) has two genetically distinct variants, including renal and systemic forms. Systemic PHA type I (PHA1B) has varying degrees of clinical presentation and results from mutations in genes encoding subunits of the epithelial sodium channel (ENaC) including the alpha, beta, and gamma subunits. To date, about 45 variants of PHA1B have been identified.

Case presentation: We report a boy with PHA1B, who presented with vomiting, lethargy, and poor feeding due to salt wasting six days after birth. The patient had electrolyte imbalances. A novel SCNN1A (sodium channel epithelial subunit alpha) gene mutation, NM_001038.6:c.1497G>C, with an autosomal recessive pattern, was identified by whole exosome sequencing. This variant was inherited as a homozygote from both heterozygous parents.

Conclusions: PHA should be considered in neonates with hyponatremia and hyperkalemia. This case report presents a patient with a novel mutation in SCNN1A that has not been previously reported. Long-term follow-up of identified patients to understand the underlying phenotype--genotype link is necessary.

Objectives: Dihydropyrimidinase deficiency is a rare autosomal recessive disorder of the pyrimidine degradation pathway, with fewer than 40 patients published. Clinical findings are variable and some patients may remain asymptomatic. Global developmental delay and increased susceptibility to 5-fluorouracil are commonly reported. Here we present atrioventricular septal defect as a novel feature in dihydropyrimidinase deficiency.

Case presentation: A four-year-old male with global developmental delay, dysmorphic facies, autistic features and a history of seizures was diagnosed with dihydropyrimidinase deficiency based on strikingly elevated urinary dihydrouracil and dihydrothymine and a homozygous pathogenic nonsense variant in DPYS gene. He had a history of complete atrioventricular septal defect corrected surgically in infancy.

Conclusions: This is the second report of congenital heart disease in dihydropyrimidinase deficiency, following a single patient with a ventricular septal defect. The rarity of the disease and the variability of the reported findings make it difficult to describe a disease-specific clinical phenotype. The mechanism of neurological and other systemic findings is unclear. Dihydropyrimidinase deficiency should be considered in patients with microcephaly, developmental delay, epilepsy and autistic traits. We suggest that congenital heart disease may also be a rare phenotypic feature.

Objectives: GH-releasing peptide-2 (GHRP2) can be used for provocative growth hormone testing (GHT). Since it acts as a powerful stimulus for GH secretion, cut-off peak GH level in GHRP2 loading test (GHRP2T) is higher than in other GHT. Nevertheless, data on response at adolescents are limited. This report aimed to investigate peak GH levels in GHRP2T in adolescents.

Methods: Clinical data of adolescents after onset of puberty who underwent GHRP2T at our institution from May 2010 to March 2023 were collected retrospectively. Subjects were classified into three groups according to underlying diseases.

Results: A total of 23 patients were included: 12 in organic or genetic GHD (o/gGHD) group, three in idiopathic GHD (iGHD) group, and eight in short stature (SS) group. The median GH peak levels were 3.4 ng/mL in o/gGHD group, 88.9 ng/mL in iGHD group, and 90.1 ng/mL in SS group, indicating a robust response of GH peak levels in iGHD and SS groups. Two patients exceeded the cut-off for GHRP2T but below for other GHT, indicating the current cut-off for GHRP2T may miss some GHD patients.

Conclusions: The GH response to GHRP2T in adolescents except the o/gGHD group may be robustly responsive. For the correct diagnosis of GHD, the cut-off peak GH levels in GHRP2T in adolescents may require revisiting.