Emre Özer

Aim: Pamidronate is the preferred treatment for osteoporosis and hypercalcemia in children. This study examined its safety and effectiveness. Material and Methods: Patients treated with pamidronate for osteoporosis and hypercalcemia were included in the study. Osteoporosis patients received 1 mg/kg/day every three months for three days, while hypercalcemia patients received a single 1 mg/kg dose. Evaluations of height, weight, body mass index, bone mineral density (BMD), fractures, biochemical data, and complications were performed before and at least six months after treatment. Results: Of the 31 patients included in the study, 21 (67.7%) were male and 10 (32.3%) were female, with a mean age of 12.20 ±4.31 years. Secondary osteoporosis was diagnosed in 20 (64.5%) patients, primary osteoporosis associated with osteogenesis imperfecta in seven (22.6%) patients, and hypercalcemia in four (12.9%) patients. The average follow-up period was 11.26 ±4.16 months. The mean BMD before treatment in patients treated with pamidronate for osteoporosis was -3.53 ±1.43, while after treatment it was -1.42 ±1.81 (p<0.001). When comparing the pre- and post-treatment periods, a decrease was observed in the total number of fractures, the number of vertebral fractures, and the number of fractures occurring more than once per year (p<0.001). Complications were observed in six (19,3%) patients but all these side effects were temporary. Conclusion: Pamidronate treatment was administered at varying doses and for differing durations to patients from multiple groups, with no significant differences in efficacy or safety observed. The low complication rates reported are consistent with the literature and substantiate the safety of the treatment.

Background/Objectives: To evaluate pancreatic size and echogenicity using ultrasonography in newly diagnosed pediatric Type 1 Diabetes Mellitus patients within five days of diagnosis, and compare early childhood (p < 0.001), with greater reductions in adolescents (head: 21%, body: 26.7%) vs. young children (head: 14.4%, body: 15.5%). Isoechoic pancreases were more common in young patients (80% vs. 40.9%; p = 0.033). C-peptide and HgbA1c were higher in adolescents (p < 0.05), with no echogenicity–autoantibody association. Conclusions: This first early-post-diagnosis ultrasonography study reveals age-specific pancreatic atrophy and echogenicity changes in children, more severe in adolescents, reflecting type 1 diabetes mellitus endotypes. Ultrasonography offers a practical noninvasive tool for early detection and endotype stratification, informing personalized diabetes care.

Objectives: Protein glycosylation is a crucial process involving the addition of oligosaccharides to proteins, which plays a significant role in stabilizing proteins and mediating protein–protein interactions. Mutations in genes associated with glycosylation can lead to congenital disorders of glycosylation (CDG), resulting in multisystem disorders. One such example is phosphoglucomutase 1 (PGM1) -CDG, caused by a deficiency of the PGM1 enzyme. In this report, we describe a patient with PGM1-CDG who was initially misdiagnosed with growth hormone insensitivity and benefited from recombinant human insulin-like growth factor-1 (rhIGF-1) therapy. Case presentation: A 2-year-11-month-old female patient, born to first-degree cousin parents, presented with hypoglycemia and short stature. Her physical examination revealed frontal bossing, infantile facial appearance, and short stature. Laboratory investigations revealed that basal and stimulated growth hormone levels were very high, IGF-1 was low, and the inadequate response to the IGF generation test was consistent with growth hormone insensitivity (GHI). The patient was started on rhIGF-1 therapy, resulting in significant height gain. Subsequently, the patient showed improvement in height with rhIGF-1 therapy. The patient, who had additional findings such as elevated creatine kinase (CK) and transaminase levels and cardiomyopathy, was diagnosed with PGM1-CDG. Conclusions: This case highlights that PGM1-CDG can mimic clinical and laboratory findings of GHI. CDG diagnosis should be considered in cases with clinical and laboratory findings of GHI accompanied by multisystem disorders such as hepatopathy, elevated CK, and cardiomyopathy. This patient’s successful response to rhIGF-1 therapy highlights the potential benefits of targeted therapies in treating growth hormone-related disorders in patients.

Objective: To investigate the frequency, etiology, and clinical characteristics of bleeding disorders (BD) in adolescents with heavy menstrual bleeding (HMB) and evaluate treatment outcomes. Methods: This retrospective study analyzed 515 adolescents (10–19 years) presenting with abnormal uterine bleeding (AUB) at a multidisciplinary clinic. After excluding 24 with chronic diseases, 491 patients were categorized as: anovulatory HMB (HMB‐An, n = 305), BD ( n = 40), and non‐HMB anovulatory cycles ( n = 146). All HMB patients underwent hemostatic and endocrine assessments, with coagulation and platelet function tests when indicated. Results: Among 345 HMB patients, 40 (11.6%) had BD. The most common cause was von Willebrand disease (vWD) (12/40, 30%), followed by coagulation factor deficiencies (11/40, 27.5%), thrombocytopenia (8/40, 20%), and platelet function defects (6/40, 15%). Hospitalization rates were higher in BD than HMB‐An (25% vs 16%). Combined oral contraceptives (0.03 mg ethinyl estradiol + 0.15 mg levonorgestrel, tapered over 7–10 days) controlled bleeding in 85% of acute‐phase HMB within a median of 3 days. VWD patients had a milder course, with fewer rates of HMB at menarche, prolonged bleeding, and transfusion needs. Conclusion: Bleeding disorders should be considered in all adolescents with HMB, particularly when hemoglobin is ≤10 g/dL. Persistent bleeding despite treatment requires re‐evaluation, even if initial results are normal, with special attention to platelet dysfunction. Early recognition and prompt initiation of hormonal therapy, especially combined oral contraceptives, effectively reduce hospitalizations, transfusions, and improve quality of life.

Objective: Small for gestational age (SGA) is a heterogeneous condition influenced by fetal, placental, maternal, and genetic factors. While most SGA children experience catch-up growth within the first two years, up to 10-15% remain short-statured and may require growth hormone (GH) therapy. This study evaluated the clinical characteristics, genetic factors, and responses to recombinant GH (rGH) therapy in non-syndromic SGA children with persistent short stature. Material and Methods: We retrospectively analyzed 36 non-syndromic short-statured children born SGA who were evaluated in a tertiary center. Genetic testing, including karyotyping and microarray analysis for copy number variations (CNVs), was performed. Growth response to rGH therapy was assessed in 19 patients over a three-year period. Results: Among the 19 patients receiving rGH therapy, the mean height SDS improved from -3.04±0.58 at baseline to -2.07±0.67 after three years, with an average gain of 0.97 SDS. CNVs were identified in 6 patients (16.66%), with several pathogenic or likely pathogenic variants, including deletions and duplications in regions associated with growth and developmental disorders. Conclusion: A significant proportion of non-syndromic SGA children with persistent short stature exhibit CNVs, underscoring the genetic complexity of this condition. rGH therapy effectively improves growth outcomes, but individual responses vary. These findings highlight the need for routine genetic screening and personalized treatment strategies to optimize care for SGA children.

Objective: Type 1 diabetes mellitus (T1DM) patients have an increased risk of developing cardiovascular disease. Our study aimed to compare epicardial fat thickness (EFT), carotid intima‐media thickness (cIMT), and arterial stiffness parameters such as pulse wave velocity (PWV), augmentation index (AI), which are well-known early markers of cardiovascular disease in adults, between children with T1DM and healthy individuals. Methods: One hundred fifteen children with T1DM and 87 age, gender, and anthropometric measurements-matched healthy children were included. The inclusion criteria for patients were having T1DM for at least 2 years and ages 8–18 years. Epicardial fat thickness and cIMT were assessed by the same pediatric cardiologist. Noninvasively, the Mobil-O-Graph® was used to evaluate PWV, AI (normalized to a heart rate of 75 beats/sec: AI@75), and the hemodynamic parameters. Results: Epicardial fat thickness and cIMT were higher (p<0.001), stroke volume and cardiac index scores were found significantly lower (p<0.001 and p=0.030, respectively) in the patient group compared with the control group. While the AI@75 was significantly higher in the patient group (p 9% group. A strong positive correlation was detected between mean cIMT and microalbuminuria (Rho=,925, p<0.01). Conclusion: These results support that children with T1DM present significant changes in important subclinical indicators for showing the development of cardiovascular disease. Cardiologic assessment of patients with T1DM can be beneficial for long-term care.

Background Menstrual irregularities are common among adolescents, often linked to anovulatory cycles. This study aims to establish diagnostic cut-off values for Polycystic Ovary Syndrome (PCOS) and differentiate these from anovulatory dysfunction in adolescents. Additionally, we assessed the sensitivity of using the Free Androgen Index (FAI) and Sex Hormone Binding Globulin (SHBG) in diagnosing PCOS. Methods This study included 305 adolescents presenting with oligomenorrhea at a tertiary center. Data were analyzed statistically and Receiver operating characteristic (ROC) curves were plotted to evaluate diagnostic performance. Results Of the 305 patients, 229 (75%) had anovulatory cycles and 36 (11.8%) had PCOS. The mean FAI values for anovulatory cycles, PCOS, and hyperinsulinism were 3.5 ± 2, 8.0 ± 5, and 8.3 ± 4, respectively (p < 0.001). A significant positive correlation was found between FAI and both HOMA-IR (r = 0.389; p < 0.001) and BMI (r = 0.499; p < 0.001). ROC analysis determined the LH threshold of 9.7 U/L and LH/FSH ratio threshold of 2.62 as predictive markers for PCOS. Conclusions Anovulatory cycles are the most frequent cause of menstrual irregularities in adolescents, with hyperandrogenism being crucial for diagnosing PCOS. The FAI may be unreliable for PCOS diagnosis due to similar values in adolescents with hyperinsulinemia and obesity. Lower SHBG levels in hyperinsulinemic obese adolescents further complicate the use of FAI, indicating that glucose/insulin metabolism significantly influences FAI/SHBG levels. Comprehensive diagnostic criteria, including androgen levels, LH/FSH ratio, SHBG, FAI levels, and ovarian ultrasound, are essential for accurate PCOS diagnosis.

Objective: The study aimed to show the clinical characteristics and prognosis of the L1 syndrome in patients with L1CAM mutations in the extracellular region. Materials and Methods: Three affected boys and their siblings and parents from a large family were included in this study. Genetic etiology was investigated by whole-exome sequencing in the index patient. The pathogenic variant was detected by whole-exome sequencing and was validated by Sanger sequencing in 3 patients and other family members. Results: We present 2 brothers and their cousin with prenatal onset hydrocephalus, severe developmental and speech delay, corpus callosum agenesis/hypogenesis, epilepsia, and adducted thumbs. A hemizygous missense mutation NM_024003 (c.A2351G:p.Y784C) on exon 18 of L1CAM gene was found in the 3 patients and their carrier mother. This missense mutation in the conserved region of the second fibronectin type III-like repeats located in the extracellular region of L1CAM resulted in the severe phenotype of X-linked inherited L1 syndrome in the patients. Conclusion: L1 syndrome should be considered in the differential diagnosis of male children with intellectual disability, hydrocephalus, and adducted thumbs. While truncating mutations of L1CAM may cause a more severe phenotype, missense mutations cause milder forms. However, pathogenic missense mutations affecting key amino acid residues lead to severe phenotype likely Cite this article as: Tüysüz B, Ercan-Şençiçek AG, Özer E, Goc N, Yalçınkaya C, Bilguvar K. Severe phenotype in patients with X-linked hydrocephalus caused by a missense mutation in L1CAM. Turk Arch Pediatr. 2022;57(5):521-525.