Journal of Clinical Research in Pediatric Endocrinology最新文献

Objective: Mandibuloacral dysplasia (MAD) is a rare genetic disorder characterized by distinctive skeletal abnormalities, metabolic issues, and skin changes, often linked to pathogenic variants in the LMNA gene, which encodes lamin A/C. This study investigates a specific founder mutation within a Turkish cohort and explores its impact on phenotypic expressivity.

Methods: We conducted a comprehensive analysis involving genetic testing for LMNA variants in patients diagnosed with MAD. Clinical evaluations documented a wide range of phenotypic features, including facial dysmorphism, skeletal anomalies, and metabolic abnormalities. We also collected family histories to assess inheritance patterns and potential environmental influences.

Results: Our findings identified a common founder mutation in the LMNA gene among the cohort, which was present in a significant percentage of participants. Notably, phenotypic expressivity varied significantly, with some individuals exhibiting classic MAD features, while others showed atypical manifestations, such as additional endocrine disorders and variable severity of skeletal anomalies. This variability underscores the complexity of the genotype-phenotype relationship.

Conclusion: This study highlights the significance of the founder mutation in LMNA and its diverse phenotypic outcomes in MAD. Our results contribute to the understanding of how genetic mutations can lead to a spectrum of clinical presentations, emphasizing the necessity for personalized clinical approaches in managing this condition. Further research is warranted to elucidate the underlying mechanisms of phenotypic variability and to improve diagnostic and therapeutic strategies.

HIST1H1E Syndrome is a rare autosomal dominant disorder resulting from a heterozygous variation in the H1-4 gene located on chromosome 6p22.2. Mental retardation, recognizable facial features, skeletal abnormalities and overgrowth are the main clinical manifestations of this syndrome. A 17-year-old male presented to the pediatric endocrinology clinic due to short stature. He had a characteristic facial appearance with neurodevelopmental delay. Genetic analysis revealed a heterozygous pathogenic variation in the H1-4 gene located on chromosome 6p22.2 which confirmed his diagnosis of HIST1H1E syndrome. In our case, distinguished by the co-occurrence of short stature and obesity accompanying central hypothyroidism and growth hormone (GH) deficiency due to hipoplastic pituitary gland, which differs from the somatic overgrowth characterizing this syndrome.These is the second reported HIST1H1E syndrome case with hyposecretion of multiple pituitary hormones caused by hypoplasia in the pituitary gland.

Thyroid cancer (TC) is the most prevalent malignancy of the endocrine system, with its incidence has been increasing worldwide in recent years. Although it generally has a favorable prognosis, aggressive forms such as anaplastic TC are associated with high mortality rates. Cell-microenvironment interactions largely influence the progression and metastatic behavior of TC; however, the precise mechanisms underlying these processes remain inadequately understood. One critical factor influencing metastasis is anoikis, a form of programmed cell death triggered by the detachment of cells from the extracellular matrix. Resistance to anoikis allows tumor cells to escape apoptosis, survive in circulation, and metastasize to distant organs. Given its pivotal role in metastasis, anoikis resistance represents a key area of study in understanding cancer progression. This review covers the molecular mechanisms and pathogenesis of TC, particularly emphasizing the role of anoikis resistance in metastatic spread and its potential as a therapeutic target.

Objective: Resistance to thyroid hormone beta (RTHβ) is a rare disorder characterized by a fairly heterogeneous clinical presentation due to varying degrees of tissue response to thyroid hormone. The present study aimed to evaluate the clinical and laboratory features and genotype-phenotype relationship of Turkish patients with RTHβ.

Methods: Patients who underwent a THRβ gene analysis between September 2019 and September 2023 were retrospectively reviewed.

Results: Fifty patients with the clinical features of RTHβ syndrome or a family history of an index case were included. A total of eight different heterozygous pathogenic/likely pathogenic missense variants, three of which were novel, were detected in THRB in 30 patients from 8 unrelated families. Although most patients with RTHβ were asymptomatic, seven patients exhibited various symptoms. Moreover, seven patients had received various treatments before diagnosis. Thyroid autoantibody was positive in 23% of all cases with a variant, and goitre was detected in 56% of children with a variant. While thyroid nodules were detected in seven adult patients, two adults had been diagnosed with papillary thyroid cancer. One child had attention-deficit disorder, learning disability, and type 1 diabetes mellitus. Of the 20 patients without a variant, TSHoma was detected in one.

Conclusion: The present study provides an overview of clinical and genetic characteristics of patients with genetically confirmed RTHβ and expanded the THRB gene variant database with three novel variants. Although most patients with RTHβ are asymptomatic, molecular genetic analysis of the THRB gene and regular follow-up because of the apparent risk of concurrent autoimmune diseases or thyroid cancer is warranted.

Objective: To evaluate the impact of continuous glucose monitoring (CGM) assistance on glycemic control in children with type 1 diabetes (T1D) in earthquake-affected regions, comparing those who benefited from CGM with those who did not. Additionally, the study assessed changes in CGM metrics over nine months of CGM use.

Methods: A multicenter, cross-sectional study was conducted across 11 centers in Türkiye. Children with T1D were divided into two groups: those who received CGM support (CGM+) and those who continued with finger-stick glucose monitoring (CGM-). Hemoglobin A1c (HbA1c) levels were measured at four intervals: pre-earthquake, 3-6 months, 6-9 months, and 9-12 months post-earthquake. In the second phase, CGM metrics were analyzed over 90-day intervals in the CGM+ group with at least 85% sensor usage.

Results: A total of 532 children were included. Median HbA1c levels decreased from 9.1% pre-earthquake to 8.8% 3-6 months postearthquake (p=0.027). In the CGM+ group, HbA1c levels significantly decreased from 8.8% to 8.3% (p<0.001), while no significant change was observed in the CGM- group. Of the 412 subjects with access to CGM reports, 105 (25.4%) had less than 85% sensor usage and were excluded. In the remaining 307 patients, there was a significant increase in active sensor time and daily glucose measurements, along with a reduction in hypoglycemia frequency over the 90-day intervals (p<0.001 for all three).

Conclusion: CGM assistance improved glycemic control in children with T1D, even under the challenging conditions following a devastating earthquake. These findings highlight the need for broader access to CGM devices to enhance diabetes management.

Cytochrome P450 17α-hydroxylase (P450c17) enzyme, encoded by the CYP17A1 gene, catalyzes 17a-hydroxylation and 17,20-lyase reactions essential for cortisol and sex steroid synthesis. 17α-hydroxylase/17,20-lyase deficiency (17OHD) is a rare autosomal recessive disease caused by CYP17A1 mutations, classified into complete and partial forms based on P450c17 defect severity. We report two unrelated girls diagnosed with 17OHD at the age of 15 and 16. Both presented with primary amenorrhea, infantile genitalia, absent axillary and pubic hair, and hypergonadotropic hypogonadism. Case 1 exhibited undeveloped breasts, nocturnal enuresis, hypertension, hypokalemia, and reduced cortisol and 17α-hydroxyprogesterone. Case 2 showed a growth spurt, spontaneous breast development, elevated corticosterone, and decreased aldosterone. Both had a 46,XX karyotype. Genetic analysis revealed a homozygous p.S106P mutation in Case 1 and compound heterozygous p.R347C/p.R362H mutations in Case 2, with the latter representing a novel combination. Based on the clinical, laboratory and genetic findings, Case 1 and Case 2 were definitively diagnosed as complete and partial forms of 17OHD, respectively. Both received estrogen and glucocorticoid replacement therapy, leading to gradual development of the uterus and breasts, and the onset of first menstruation. In Case 1, hypertension, hypokalemia, and nocturnal enuresis were significantly alleviated. In conclusion, we report the first case of complete 17OHD accompanied by nocturnal enuresis and identify a novel compound heterozygote (p.R347C / p.R362H) of CYP17A1 gene in a case of partial 17OHD.

Objective: To date, muscle strength and thickness have not been investigated in adolescents with polycystic ovary syndrome (PCOS). This study aimed to investigate whether differences exist in these parameters between adolescents with PCOS and healthy controls. Additionally, we evaluated the effects of six months combined oral contraceptive (COC) treatment on quadriceps muscle characteristics.

Methods: The study included adolescents diagnosed with PCOS and healthy peers. Dynamometers were used to measure knee muscle and hand grip strengths, and ultrasound was used to measure quadriceps muscle thickness. In the PCOS group, all measurements were repeated after six months of COCs treatment.

Results: There were 20 participants in each of the PCOS and control groups. There were no significant differences between the groups in terms of age, weight, height, pubertal stage, Physical Activity Questionnaire scores, quadriceps muscle thickness, grip strength and isokinetic knee strengths at baseline. Within the PCOS group, significant increase were observed in weight, height, quadriceps strength and lipid levels after six months of treatment (all p<0.05). Subgroup analysis of COC treatments revealed significantly greater gains in quadriceps muscle strength among levonorgestrel users (n=6) compared to those using cyproterone acetate users (n=13).

Conclusion: Quadriceps muscle thickness and strength were comparable between adolescent with PCOS and controls, indicating no intrinsic muscular deficit. However, significantly greater improvements in quadriceps muscle strength were observed in those using levonorgestrel-containing COCs users compared to cyproterone acetate users. These findings suggest a potential role of progestin androgenicity in muscle strength. Further longitudinal studies with larger cohorts are warranted to validate these preliminary findings and to explore the impact of COCs with varying androgenic properties.

Objective: The Menstrual Bleeding Questionnaire (MBQ) is a scale developed to identify women with heavy menstrual bleeding. The aim was to evaluate the validity/reliability of the Turkish version of this scale.

Methods: The MBQ was translated into Turkish and adapted to the adolescent age group. Face validity of the draft scale was tested by piloting. To ensure concurrent validity, MBQ was first applied together with the Short Form-36 (SF-36). Afterwards, both questionnaires were given to adolescent girls and the reliability of the scale was evaluated by retesting in a subgroup.

Results: The pilot study was performed with ten adolescent girls, median age 14.5 (13-16) years. The main follow-up reliability study included 251 girls medan age 16 (11-18) years, of whom 63 (25.1%) underwent retesting. There was a strong correlation between the results of the first MBQ and the second MBQ. The reliability coefficients of both the SF-36 and MBQ were above the acceptable limit of 0.70. Kaiser-Meyer-Olkin (KMO) sampling adequacy for the first application of the MBQ was above the good level (KMO=0.831, p<0.001). Eigen values of 48.73% were determined in four factors. When the pattern matrix of the first application of MBQ was examined, distribution of the items was generally regular. Receiver operator characteristics analysis of the MBQ values showed areas under the curve of the symptom effect (0.882), symptom (0.884) and severity (0.903) sub-dimension values were high. MBQ results revealed abnormal uterine bleeding in 11/251 (4.3%) cases.

Conclusion: This Turkish adaptation of the MBQ demonstrated good internal consistency, high reliability, and acceptable validity. Using it with adolescent Turkish girls will facilitate evaluation of conditions associated with abnormal uterine bleeding.

Objective: To compare serum mitochondrial open reading frame of 12S rRNA-c (MOTS-c) levels, a new potential biomarker for oxidative stress, in children with type 1 diabetes mellitus (T1DM) and healthy children. A further aim was to investigate serum MOTS-c levels as a potential early indicator of diabetic kidney disease (DKD) by correlating levels with changes in glomerular filtration and microalbuminuria.

Methods: Patients with a diagnosis of T1DM and healthy controls were recruited. MOTS-c, urinary albumin excretion, estimated glomerular filtration rate (eGFR), and hemoglobin A1c (HbA1c) were evaluated and clinical features and anthropometric measurements were collected. Patients were stratified according to diabetes duration, presence of albuminuria, glomerular hyperfiltration, eGFR decline and metabolic control.

Results: The T1DM group included 82 [female:male (F:M) 1:1.64] patients while the controls numbered 61 (F:M 1:0.97), with respective mean ages of 14.3±3.3 and 10.6±4.2 years (p<0.01). MOTS-c levels were significantly lower in the T1DM group than controls (76.2±1.3 vs 105.2±7.0, p<0.001). No difference was found in MOTS-c levels between patient subgroups categorized by diabetes duration, obesity, metabolic control, hypertension, hyperlipidemia, glomerular hyperfiltration, decline in eGFR, and presence of microalbuminuria. Simple linear regression indicated that MOTS-c was not predictive for DKD.

Conclusion: MOTS-c levels were lower in children with T1DM than in healthy children. However, the lack of association of MOTS-c with renal biomarkers suggested that it is not an effective early marker for DKD. However, this finding suggests that the onset of oxidative damage and mitochondrial dysfunction in T1DM is independent of DKD. In addition, the results suggests that HbA1c and duration of diabetes are significant risk factors for development of microalbuminuria, while changes in eGFR and microalbuminuria continue to serve as indicators of DKD.

Objective: To evaluate the off-label use of the MiniMed™ 780G system in children under seven years old, as clinical outcomes in this age group are less well-established, despite the improvements in glycemic control seen with MiniMed™ 780G therapy.

Methods: Children under seven years old with type 1 diabetes using MiniMed™ 780G pump therapy were compared with children of similar age and gender using MiniMed™ 640G insulin pump therapy and multiple-dose insulin therapy with continuous glucose monitoring systems (CGMs). CGM metrics, total daily insulin (TDI) dose, and hemoglobin A1c (HbA1c) levels were evaluated retrospectively at baseline and at the 3^rd, 6^th, and 12^th months.

Results: At the initiation of MiniMed™ 780G therapy, the mean age was 5.25±1.22 years (range: 2.8-6.8 years), and the mean TDI was 10.12±4.34 U/day (range: 4.5-17.0 U/day). The glucose management indicator and HbA1c remained lower in the MiniMed™ 780G group at the 3^rd, 6^th, and 12^th months compared to baseline (p=0.009 and p<0.001, respectively). In the MiniMed™ 780G group, time above range (TAR) was significantly lower at the 3^rd, 6^th, and 12^th months (p=0.018, p=0.017 and p=0.04, respectively) while time in range (TIR) was higher at the 3^rd, and 12^th months (p=0.026 and p=0.019, respectively) compared to other groups. The coefficient of variation (CV) of the sensor glucose and HbA1c were lower at the 12th month (p=0.008 and p=0.015, respectively) compared to both other groups. No instances of ketoacidosis or severe hypoglycemic events were observed in any of the children during the follow-up period.

Conclusion: The absence of significantly higher levels of hypoglycemia compared to other groups at any time point, along with a significant decrease in TAR across all time points, a significant increase in TIR at the 3^rd and 12^th months, and a significant decrease in HbA1c and CV suggests that the MiniMed™ 780G system is both safe and effective for children under seven years old.