Journal of Clinical Research in Pediatric Endocrinology最新文献

Biallelic FKBP10 variants cause autosomal recessive osteogenesis imperfecta(OI) type XI (OI-XI) and Bruck syndrome type 1 (BS-1), both characterized by bone fragility. However, BS-1 is additionally marked by joint contractures, leading to diagnostic overlap with OI-XI. To present two FKBP10-related cases illustrating the phenotypic continuum and diagnostic challenges between BS-1 and OI-XI. Case 1, a 3.5-month-old male, had multiple fractures, progressive joint contractures, and scoliosis. Genetic testing revealed a novel homozygous FKBP10 variant, c.603T>A (p.Tyr201Ter), confirming BS-1. Case 2, a 13-day-old male, presented with recurrent fractures but no contractures or pterygium. A pathogenic homozygous FKBP10 variant, c.890_897dupTGATGGAC (p.Gly300Ter), confirmed OI-XI. Despite bisphosphonate therapy, the BS-1 case continued to experience fractures, whereas the OI-XI patient remained fracture-free with improved bone mineral density. These cases demonstrate that FKBP10-related disorders represent a phenotypic continuum rather than distinct entities. Long-term follow-up is crucial, as BS-1 features such as contractures and scoliosis may become more evident or progressive over time. Recognition of evolving phenotypes is essential for accurate diagnosis and management.

Objective: Nutrition can affect visceral adipose tissue, but the effect of dietary diversity on visceral adiposity is unknown. This study aimed to determine the relationship between dietary diversity and visceral adiposity, triglyceride/glucose, lipid accumulation product, and body shape indices in obese adolescents.

Methods: The study included 141 obese adolescents (70 males, 71 females) aged between 12 and 18. Participants' biochemical parameters, anthropometric measurements, and blood pressures were measured. Two days of retrospective food intake records were collected from the adolescents, and Dietary Diversity Scores (DDS) were calculated and divided intotertiles.. A DDS score of <4.09 was classified as tertile 1; 4.09-4.96 as tertile 2; and >4.96 as tertile 3. Visceral adiposity, triglyceride/glucose, lipid accumulation product, and body shape indexes were calculated according to the formulas specified in the literature.

Results: Insulin and Homeostasis Model assessment for Insulin Resistance (HOMA-IR) values were found to be higher in individuals in Tertile 1 compared to those in other tertiles (p<0.001). The triglyceride/glucose index value was found to be lower in individuals in Tertile 3 compared to those in Tertile 1 (p=0.028). In individuals in Tertile 3, fibre (p=0.002), vegetable (p<0.001), and whole grain (p<0.001) intake were higher than in other tertiles, while refined grain (p<0.001) and meat consumption (p=0.013) were lower than in other tertiles. A negative correlation was found between the DDS and fasting blood glucose (rho = -0.177; p = 0.036), insulin (rho = -0.633; p < 0.001), triglycerides (rho = -0.223; p = 0.008), HOMA-IR (rho = -0.656; p < 0.001), visceral adiposity index (rho = -0.228; p = 0.007), triglyceride/glucose index (rho = -0.251; p = 0.003), and lipid accumulation product index (rho = -0.200; p = 0.018). When confounding factors were controlled for, fasting blood glucose emerged as the significant factor affecting DDS.

Conclusion: High dietary diversity scores in obese adolescents are associated with low visceral adiposity, triglyceride/glucose, and lipid accumulation product index, indices associated with visceral obesity. As dietary diversity scores increase, fasting blood sugar, insulin, triglyceride, and HOMA-IR levels decrease.

18p deletion syndrome is a rare chromosomal disorder that can present with a wide range of phenotypic features and is occasionally associated with autoimmune diseases. We report the case of a 3-year and 8-month-old girl who presented with polydipsia and polyuria and was subsequently diagnosed with type 1 diabetes mellitus (T1DM) based on clinical and laboratory findings. The patient exhibited dysmorphic facial features and developmental delay, leading to genetic testing, which revealed a 13.7 Mb deletion on the short arm of chromosome 18 (18p11.32p11.21). Over the following years, she developed additional features, including Hashimoto's thyroiditis, epilepsy, subaortic stenosis requiring surgical resection, IgA deficiency, bilateral sensorineural hearing loss, and myopia. Genetic analysis also identified the deletion of several potentially disease-modifying genes, including PTPN2, PTPRM, LPIN2, USP14, and ADCYAP1. This case highlights the potential role of genes within the 18p region in the pathogenesis of autoimmune endocrinopathies. It supports further investigation into the immunogenetic mechanisms in 18p deletion syndrome.

Familial hypertriglyceridemia (FHTG) is a rare inherited lipid disorder that may present with severe phenotypes when caused by compound heterozygous or biallelic APOA5 variants. We report a male child diagnosed at 2.5 years of age with severe hypertriglyceridemia, who exhibited serum triglyceride levels persistently above 10 mmol/L (≈ 885 mg/dl) despite adherence to a low-fat diet and pharmacotherapy including fibrates, omega-3 fatty acids, and statins. Representative triglycerides at presentation were 11.6 mmol/L (≈ 1029 mg/dl). During follow up, the patient experienced an acute abdominal pain episode with triglycerides nearing 20 mmol/L (≈ 1770 mg/dL), managed conservatively under suspicion of pancreatitisOral glucose tolerance testing showed a high-normal insulin response (peak 84.5 mIU/L, below the insulin-resistance threshold of 100-150 mIU/L), which prompted addition of metformin. Over a decade, despite normal growth and clinical well-being, biochemical control remained suboptimal. This case illustrates the clinical utility of early genetic testing in pediatric dyslipidemias and highlights limitations of traditional treatments in monogenic severe FHTG. Emerging therapies, including antisense oligonucleotides and ANGPTL3 inhibitors, may hold future promise.

Autosomal dominant hypophosphatemic rickets (ADHR) is a rare metabolic bone disease with variable clinical presentation, caused by pathogenic variants in the FGF23 gene. The disease typically manifests in childhood with growth retardation and rickets symptoms, but may also be diagnosed in adolescence or adulthood with atypical symptoms. We present a 14-year and 5-month-old female patient who presented with bilateral sacral insufficiency fractures following a subtle onset without a history of trauma. Diagnostic tests revealed findings consistent with hypophosphatemic rickets and a de novo heterozygous c.526C>T (p.Arg176Trp) variant in the FGF23 gene, leading to a diagnosis of ADHR. The patient had no significant history of rickets during childhood. She had lived for approximately one year with complaints of progressive pain in the lower lumbar region, which worsened with walking and sitting, without receiving a diagnosis. Bilateral sacroiliac insufficiency fractures and hypophosphatemia were detected, and genetic analysis was performed. The patient underwent bilateral sacroiliac fracture fixation by pediatric orthopedics, and phosphate and active vitamin D (calcitriol) therapy was initiated by pediatric endocrinology. Clinical symptoms improved significantly during follow-up. Due to its genetic and clinical heterogeneity, autosomal dominant hypophosphatemic rickets (ADHR) is a disease that can cause delays in diagnosis. The number of cases reported in the literature associated with this variant is limited, and this is, to the best of our knowledge, the first report of an adolescent with ADHR diagnosed with bilateral sacral insufficiency fractures. This case is important for raising awareness of ADHR and highlighting the broad clinical spectrum of the disease. Sharing the diagnostic and treatment processes will be helpful for clinicians encountering this rare disease.

Introduction: Complete Androgen Insensitivity Syndrome (CAIS) is caused by mutations in the androgen receptor gene (AR), leading to androgen resistance. Early recognition is crucial for management. To evaluate clinical presentations, hormonal profiles, genetic characteristics, and decisions regarding gonadectomy in pediatric CAIS. Factors influencing gonadectomy, including malignancy risk, gonadal function, and psychological well-being were assesed.

Material and methods: Medical records of 16 children genetically confirmed CAIS patients, aged 3 days-18 years, diagnosed between 2004 and 2024 at a tertiary referral center were retrospectively reviewed. Clinical, hormonal, genetic, and histological data were analyzed.

Results: Twelve patients (75%) were diagnosed prepubertally, most commonly due to inguinal hernia. Familial recurrence occurred in 4 cases (25%). Novel pathogenic AR variants not previously reported in public databases were identified in three patients. Prepubertal patients with hormone data (n=5) demonstrated AMH >150 pM. Pubertal patients (n=9) had markedly elevated testosterone levels [median at 1361.3 ng/dl, range 367-3460 ng/dl]. Gonadal biopsy was performed in 3 cases (19%). Gonadal preservation was recommended in 11 children (69%), while 5 (31%) underwent gonadectomy followed by estrogen replacement therapy.

Conclusions: Most CAIS cases in this pediatric cohort were detected early through inguinal hernia or family screening. Delayed gonadectomy allowed spontaneous pubertal development and feminization. While gonadectomy results in lifelong hormone dependence and may raise identity-related concerns, surveillance-based gonadal preservation appears safe during childhood. The identification of novel AR variants expands the mutational spectrum of CAIS and highlights the need for multicenter registries and improved biomarkers to optimize individualized care.

Coexistence of Type 1 diabetes mellitus (T1DM) with glucokinase maturity-onset diabetes of the young (GCK-MODY) is extremely rare. Herein, we reported a case, conducted a systematic review and summarized the other reported cases to enhance the awareness of this rare diabetes subtype. An 11-year-old boy was presented with polydipsia, polyuria, and weight loss. He was diagnosed with T1DM based on significant hyperglycemia, decreased C-peptide levels, and positive diabetes-related antibodies. Genetic testing revealed that both the patient and his father carried a heterozygous mutation in the GCK gene. Due to the coexistence of GCK-MODY, the patient experienced difficulties in glycemic control and frequent hypoglycemia during insulin therapy. The patient's father gradually reduced and discontinued insulin treatment after genetic test. In clinical practice, the possibility of overlapping diabetes types should be highly emphasized. Genetic testing should be performed to optimize treatment plans and improve patient outcomes.

Background: The absence of newborn screening, insufficient knowledge among medical professionals, and poor treatment adherence in Congenital Adrenal Hyperplasia (CAH) in Indonesia caused late diagnosis. This study presents two decades of experience in gender assignment and diagnosis of 46,XX CAH.

Methods: A cohort study was carried out at a CAH referral center in Central Java, Indonesia. Data regarding clinical outcomes, molecular analysis, and sociodemographic information were taken from medical records. Participants were grouped based on current gender, i.e., females and males. Gender at diagnosis, age at first presentation, age at first diagnosis, age at present, CAH types, virilization, puberty, birth attendant, and gender at birth decision maker significantly predict current gender identity.

Results: Among 131 individuals with 46,XX CAH, 52 (52/131) with a sex assignment incongruent with their karyotype were included. The majority (49/52) had 21-hydroxylase deficiency (21OHD), while three (5.77%) had 11 beta-hydroxylase deficiency (11OHD). Individuals assigned as males at birth (3/52) had severe virilization. A change of gender occurred in 46 of 52 patients (88.46%). Midwives were the most frequent birth attendants (24/51), while pediatricians were the major decision-makers (19/51) of sex assignment.

Conclusion: In Indonesia, many 46,XX individuals with CAH were initially assigned as males due to late diagnosis, primarily caused by low awareness among healthcare professionals and exacerbated by limited medical resources and a lack of clear guidelines on sex assignment. Therefore, targeted education and standardized guidelines involving a multidisciplinary team are crucial to ensure appropriate sex assignment and care.

Background: Hypoglycaemia is one of the comorbidities that adversely affects the quality of life in patients with cystic fibrosis (CF). Isolated hypoglycaemia (IsoHypo) is poorly described in patients with CF and its aetiopathogenic significance is unclear.

Aim: To investigate the etiopathogenesis of IsoHypo and the role of pancreatic insufficiency (PI) in IsoHypo in children with CF.

Patients and methods: The blood glucose, insulin, and glucagon responses of 44 patients with CF and 9 healthy controls were evaluated during a 3-hour oral glucose tolerance test. Based on the results, the patients were categorized into 5 groups: 1) normal glucose tolerance (NGT), 2) IsoHypo, 3) hypoglycaemia with abnormal glucose tolerance (Hypo+AGT), 4) AGT, and 5) CF-related diabetes. IsoHypo and NGT were sub-classified according to the presence of PI as PI(+) or PI(-). Hypoglycaemia was defined as <70 mg/dL.

Results: Hypoglycaemia was observed in 21 of 44 patients (47.7%), predominantly as IsoHypo (29.5%). Hypo+AGT was found in 8 patients (18.2%). The IsoHypo group showed undelayed and higher insulin secretion than the Hypo+AGT group, especially in IsoHypo PI(-) compared to IsoHypo PI(+). Both IsoHypo and Hypo+AGT groups exhibited an insufficient increase in glucagon at 180 minutes, with the deficiency being more pronounced in the Hypo+AGT group. Insulin and glucagon responses to oral glucose load in IsoHypo PI(+) were similar to Hypo+AGT, whereas they were less affected in IsoHypo PI(-) patients who had early and higher insulin secretion.

Conclusion: IsoHypo is common in CF children and might precede Hypo+AGT in those with pancreatic insufficiency. The abnormal insulin and glucagon responses to glucose are the most significant contributors to the development of IsoHypo in CF.

Background: Endocrine findings in premature adrenarche have been characterized by elevated DHEAS levels in the past.

Methods: We reviewed 44 female patients, aged 4 to 8 years, with premature adrenarche who were seen at our center between 2019 and 2023. Data were collected on the traditional androgens (DHEA and DHEAS) and novel 11-oxo-androgens. 11-oxo-androgens, DHEAS, and DHEA levels were measured using Liquid chromatography/tandem mass spectrometry (LC/MS-MS) assays in commercial laboratories (Lab Corp).

Results: The majority, 89% of patients from the youngest group (4-5year olds), presented with apocrine odor as the only symptom of premature adrenarche. We have demonstrated that DHEA and DHEAS levels were within the normal range in many girls with premature adrenarche, whereas 11-oxo-androgens, particularly 11-hydroxyandrostenedione and 11β-hydroxytestosterone, were elevated. Out of those with normal DHEAS, 75 % had elevated 11-hydroxyandrostenedione, and 77.8% of those patients with normal DHEA had the same elevated oxo-adrogen. Additionally, advanced bone age greater than 1 year compared to chronological age was positively associated with 11-ketotestosterone (Spearman correlation coefficient = 0.32, 95% CI: 0.01-0.57, p=0.0429) and 11β-hydroxy testosterone (Spearman correlation coefficient=0.32, 95% CI: 0.01-0.58, p=0.0395).

Conclusion: We propose that 11-oxoandrogens are a more sensitive steroid to be measured in premature adrenarche.