Journal of pediatric endocrinology & metabolism : JPEM最新文献

{"title":"A case of JAGN1 mutation presenting with atypical diabetes and immunodeficiency.","authors":"Céline De Cuyper, Willem Staels, Siel Daelemans, Jesse Vanbesien, Elise Nauwynck, Inge Gies","doi":"10.1515/jpem-2025-0065","DOIUrl":"https://doi.org/10.1515/jpem-2025-0065","url":null,"abstract":"<p><strong>Objectives: </strong>To describe the case of a young girl with severe congenital neutropenia caused by a homozygous variant in the Jagunal homolog 1 (<i>JAGN1</i>) gene, who later developed atypical diabetes.</p><p><strong>Case presentation: </strong><i>JAGN1</i> deficiency disrupts neutrophil maturation, resulting in immunodeficiency and recurrent infections. Our patient also exhibited impaired humoral immunity, requiring immunoglobulin replacement therapy, which reduced infection frequency. Several years after the identification of her <i>JAGN1</i> mutation, she developed atypical insulin-dependent diabetes mellitus - a condition not previously associated with <i>JAGN1</i> mutations. This novel finding suggests a potential role for <i>JAGN1</i> in pancreatic β-cell function.</p><p><strong>Conclusions: </strong>This case expands the spectrum of <i>JAGN</i> <i>1</i>-related immune dysfunction and introduces a potential link between <i>JAGN1</i> deficiency and diabetes. We explore possible mechanisms underlying this association, highlighting the need for further research. Clinicians should consider <i>JAGN1</i> mutations in the differential diagnosis of combined immune and metabolic disorders.</p>","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144669276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding rickets in osteopetrosis via a case: mechanisms and treatment implications.","authors":"Meliha Esra Bilici, Zeynep Şıklar, Elif Özsu, Serdar Ceylaner, Zehra Aycan, Rukiye Uyanık, Merih Berberoğlu","doi":"10.1515/jpem-2025-0145","DOIUrl":"https://doi.org/10.1515/jpem-2025-0145","url":null,"abstract":"<p><strong>Objective: </strong>Osteopetrorickets is a rare autosomal recessive disease that affects many systems and is characterized by dense bone mass and paradoxical rickets due to insufficient resorption of calcified cartilage. Its rarity and presentation with nonspecific symptoms may cause delays in diagnosis. Early diagnosis and improvement of rickets accompanying bone marrow transplantation as a curative treatment option before the development of any irreversible complications are essential for prognosis. However, the etiopathogenesis and management of rickets treatment strategies are still controversial.</p><p><strong>Case presentation: </strong>A 4-month-old female patient, whose loss of vision had been followed for 1.5 months, was admitted to our clinic with the request for a disability report. Clinical and laboratory findings were consistent with osteopetrorickets. Molecular analysis revealed a homozygous variant in the <i>TCIRG1</i> gene. She was normocalcemic and hypophosphatemic, and the 25-OH vitamin D level was normal, while 1.25-dihydroxyvitamin D levels were quite high. Treatment was started with low-dose calcium replacement and calcitriol. The dose of calcitriol was gradually increased to 300 ng/kg/d, and a significant clinical response was achieved. Bone marrow transplantation was conducted at 8 months postnatally from an HLA-compatible non-related donor; nonetheless, the patient succumbed to respiratory problems on the 71st day following the procedure.</p><p><strong>Conclusion: </strong>Nonspecific symptoms of osteopetrorickets should be considered for early diagnosis, as a timely intervention in the first months of life can be life-saving. The pathophysiology of rickets remains unclear, but low calcium-phosphorus product and resistance to 1.25-dihydroxyvitamin D appear to play key roles. High-dose calcitriol and cautious calcium supplementation may improve outcomes, though further research is needed to optimize treatment strategies.</p>","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144645206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic, neuroimaging, and clinical characteristics of a cohort of individuals with L-2-hydroxyglutaric aciduria from Türkiye.","authors":"Ayşenur Engin Erdal, Sümeyra Zeynep Özbey, Gülten Burcu Civelek Ürey, Aynur Küçükçongar Yavaş, Berrak Bilginer Gürbüz, Mehmet Gündüz, Esra Kiliç, Avni Merter Keçeli, Aydan Değerliyurt, Çiğdem Seher Kasapkara","doi":"10.1515/jpem-2025-0021","DOIUrl":"https://doi.org/10.1515/jpem-2025-0021","url":null,"abstract":"<p><strong>Objectives: </strong>L-2-hydroxyglutaric aciduria (L2HGA) is a hereditary metabolic disorder characterized by the accumulation of L-2-hydroxyglutaric acid in body fluids, particularly in cerebrospinal fluid, which disrupts neuron function in the central nervous system and triggers oxidative stress. It can cause seizures, developmental disorders, and behavioral abnormalities.</p><p><strong>Methods: </strong>The study retrospectively evaluated the demographic information, initial symptoms, clinical characteristics, cranial magnetic resonance imaging (MRI) findings, and post-treatment biochemical changes of 10 cases diagnosed with L2HGA.</p><p><strong>Results: </strong>The study included five paediatric and five adult cases with a molecular diagnosis of L2HGA. The mean age at diagnosis was 10.1 years. Convulsion was identified as the primary presenting symptom in 70 % of cases. We identified intellectual disability in 80 % of our cases. In addition to the classic cranial MRI findings of subcortical white matter involvement, basal ganglia involvement was detected in 60 % of cases. We found that 2-hydroxyglutaric acid levels in urine organic acid analysis were significantly decreased riboflavin and carnitine post-treatment, with a mean decrease of 133.89 ± 101.43 mmol/mol creatinine (p=0.017). The most common missense variant identified in the <i>L2HGDH</i> gene was c.905C>T (p.Pro302Leu), occurring at a frequency of 50 % (5/10). The cases did not report significant improvement in their symptoms with treatment.</p><p><strong>Conclusions: </strong>L2HGA is a rare metabolic disorder that is more common in communities where consanguineous marriages are prevalent. Early diagnosis enables early treatment and protection of the brain from oxidative stress. As more cases are reported publicly, studies on genotype-phenotype relationships will yield more significant findings.</p>","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144639575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>GNB1</i> haploinsufficiency presents as monogenic obesity syndrome.","authors":"Pankaj Prasun, Katelyn J Watkin","doi":"10.1515/jpem-2025-0020","DOIUrl":"https://doi.org/10.1515/jpem-2025-0020","url":null,"abstract":"","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144593780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Performance of adult height prediction methods in 6 to 8-year-old girls with GnRH-dependent precocious puberty.","authors":"Anni Erkko, Matti Hero, Tero Varimo, Taneli Raivio","doi":"10.1515/jpem-2024-0608","DOIUrl":"https://doi.org/10.1515/jpem-2024-0608","url":null,"abstract":"<p><strong>Objectives: </strong>In girls with precocious puberty (PP), adult height prediction (PAH) is crucial in treatment planning, yet the estimations may be prone to inaccuracies. This study aimed to compare the accuracy of two commonly used PAH methods in 6-8-year-old girls diagnosed with idiopathic GnRH-dependent PP.</p><p><strong>Methods: </strong>This retrospective study included data on 60 six- to eight-year-old girls diagnosed with PP. Data was collected from medical records. Forty-eight (82 %) girls were treated with GnRH analogues, and 18 (30 %) had data on AH. Bone ages (BA) were assessed with Greulich-Pyle and BoneXpert. PAHs were estimated with Bayley-Pinneau and BoneXpert.</p><p><strong>Results: </strong>In girls treated with GnRH-analogue, AH did not significantly differ from the mean PAH calculated by Bayley-Pinneau (mean difference, -0.1 cm ± 6.6 cm (SD); p=0.93). Predicted adult height estimated by BoneXpert was higher than the actual AH (-3.6 cm ± 4.6 cm, p=0.01), but it showed lower variability in individual prediction errors and less bias related to the degree of BA advancement than Bayley-Pinneau. All subjects reached their mid-parental target height range.</p><p><strong>Conclusions: </strong>In 6- to 8-year-old girls with signs of idiopathic GnRH-dependent precocious puberty, the potential to reach their growth target remains, and overestimation of residual height growth at diagnosis should be carefully considered before initiating treatment.</p>","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144593781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the impact of androgen levels on depression and anxiety in adolescent females: a clinical perspective.","authors":"Emel Hatun Aytaç Kaplan, Yasin Çalişkan, Zümrüt Kocabey Sütçü","doi":"10.1515/jpem-2024-0491","DOIUrl":"https://doi.org/10.1515/jpem-2024-0491","url":null,"abstract":"<p><strong>Objectives: </strong>Depression and anxiety are rare disorders that can be seen in childhood. Anxiety disorders are more common. The underlying causes of these mental disorders are generally unknown. Changes in the body caused by hyperandrogenism may lead to mental disorders. In this study, we investigated the association of androgen excess with depression and anxiety in adolescent girls.</p><p><strong>Methods: </strong>Adolescent girls with elevated androgen levels were evaluated using the DSC and SCARED scales and underwent a child psychiatric evaluation. Physical examination and the relationship between scale scores and anxiety and depression were investigated.</p><p><strong>Results: </strong>Fifty-three girls aged 10-18 (mean 15.09 ± 1.26) with androgen elevation participated in the study. In our study, the frequency of panic disorder, separation anxiety, and eating disorders was shallow, but the frequency of generalized anxiety, social anxiety, and depression was high (21 %, 29%, 23 %). None of our patients had school phobia, bipolar disorder, suicidality, obsessive-compulsive disorder, enuresis, or encopresis. No significant change was observed in scale scores with any androgen elevation.</p><p><strong>Conclusions: </strong>In our study, we found that androgen elevation did not change the frequency of mental disorders in adolescent girls. Despite the large number of studies, it is still controversial whether hyperandrogenemia increases mental disorders due to conflicting results between studies.</p>","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144546856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prolonged symptom duration and the potential for gradual progression in pediatric adrenocortical tumors: observations from the MET studies.","authors":"Michaela Kuhlen, Stefan A Wudy, Clara Baumann, Christian Vokuhl, Michaela F Hartmann, Marina Kunstreich, Rainer Claus, Antje Redlich","doi":"10.1515/jpem-2025-0198","DOIUrl":"https://doi.org/10.1515/jpem-2025-0198","url":null,"abstract":"<p><strong>Objectives: </strong>To explore the clinical spectrum and symptom duration in pediatric adrenocortical tumors (pACTs), with a focus on identifying cases that may reflect gradual tumor progression.</p><p><strong>Methods: </strong>We retrospectively analyzed data from 110 pediatric patients with pACTs enrolled in the German Pediatric Oncology Hematology-Malignant Endocrine Tumor (GPOH-MET) studies (1997-2022). Endocrine symptom duration, histopathological classification, and clinical outcomes were assessed. Patients with symptom durations ≥2 standard deviations (SDs) from the mean were defined as outliers and evaluated for potential progression.</p><p><strong>Results: </strong>The cohort included 31 patients with adrenocortical adenomas (ACAs), 12 with tumors of uncertain malignant potential (ACx), and 67 with adrenocortical carcinomas (ACCs). Seven patients (6.4 %) showed markedly prolonged symptom duration, including four with ACC. One representative case demonstrated a nearly 5-year course from initial androgen excess to metastatic ACC, with evolving biochemical features and a diagnostic urinary steroid profile indicative of adrenal tumor activity.</p><p><strong>Conclusions: </strong>A small subset of pACTs may present with prolonged endocrine symptoms, possibly reflecting gradual tumor evolution. While molecular validation is lacking, these findings support the need for early recognition and further research into the natural history of pACTs.</p>","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144513061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transient worsening of thyrotoxic myopathy following methimazole and metoprolol initiation in a 12-year-old girl: a case report and literature review.","authors":"Yuto Onishi, Shinji Higuchi, Kohei Iwata, Yoh Watanabe, Yuki Yamada, Jun Mori","doi":"10.1515/jpem-2025-0205","DOIUrl":"https://doi.org/10.1515/jpem-2025-0205","url":null,"abstract":"<p><strong>Objectives: </strong>Thyrotoxic myopathy (TM) is a muscle disorder associated with hyperthyroidism. Although TM is common in adults, its incidence in children is unknown due to the limited number of reports. TM usually improves with the treatment of hyperthyroidism. This is the first report of a patient with TM who experienced transient worsening of muscle weakness shortly after administration of methimazole (MMI) and metoprolol tartrate.</p><p><strong>Case presentation: </strong>A 12-year-old Japanese girl with Graves' disease was administered MMI and metoprolol tartrate. Within 12 h of treatment initiation, the patient experienced difficulty in standing from a chair. Examination revealed proximal lower-limb weakness and reduced grip strength. Based on the patient's clinical course and blood test results, thyrotoxic periodic paralysis, myasthenia gravis, or polymyositis were considered unlikely. While the side effects of MMI and metoprolol tartrate were also considered as differential diagnoses, her history revealed mild pre-existing lower limb muscle weakness for 2 months before treatment, suggesting that the side effects of the medication were unlikely. Given the clinical course, the worsening of TM was the most probable cause, and treatment was continued cautiously. Muscle weakness gradually improved over 3 months as her thyroid hormone levels normalized. Magnetic resonance imaging taken 1 month later revealed gluteus muscle atrophy, which resolved within 10 months.</p><p><strong>Conclusions: </strong>TM may show transient worsening after MMI and metoprolol tartrate administration, requiring the evaluation of TM, drug side effects, and other possible causes before continuing treatment. This case highlights the importance of recognizing TM in pediatric patients.</p>","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Caudal epidural steroid injection as a novel therapy for treatment-induced neuropathy of diabetes in children: report of two cases.","authors":"Anju Bala, Babita Ghai, Arun George, Sayan Banerjee, Mohit Kumar, Devi Dayal","doi":"10.1515/jpem-2025-0005","DOIUrl":"https://doi.org/10.1515/jpem-2025-0005","url":null,"abstract":"<p><strong>Objectives: </strong>Treatment-induced neuropathy of diabetes (TIND) is a rare complication of rapid glycemic improvement, characterized by severe shooting pain, predominantly in the lower extremities. This report aims to highlight the clinical presentation of TIND and evaluate the effectiveness of caudal epidural steroid injections (CESI) in managing refractory pain in pediatric cases.</p><p><strong>Case presentation: </strong>We describe two pediatric cases of TIND following rapid improvement in glycemic control for type 1 diabetes. Both patients presented with debilitating pain and sleep disturbances that severely impacted their daily activities. Initial management with a combination of analgesics, pregabalin, gabapentin, and duloxetine failed to provide adequate relief. Subsequently, both patients received CESI with bupivacaine and methylprednisolone. Significant symptomatic improvement in pain and sleep was observed within 4-6 weeks post-intervention. At the 6-month follow-up, the pain relief was sustained, and no adverse effects were reported.</p><p><strong>Conclusions: </strong>These cases underscore the importance of recognizing TIND as a potential complication of rapid glycemic control and the challenges in its management. CESI appears to be a promising therapeutic option for children with refractory TIND, offering durable pain relief and improved quality of life. Further studies are needed to validate its efficacy and safety in larger cohorts.</p>","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144328447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Height velocity in the detection of growth disorders reconsidered: a retrospective analysis of the DONALD study.","authors":"Ibrahim Duran, Maja Zimmermann, Jonathan Buggisch, Heike Hoyer-Kuhn, Ute Alexy, Eckhard Schoenau","doi":"10.1515/jpem-2025-0225","DOIUrl":"https://doi.org/10.1515/jpem-2025-0225","url":null,"abstract":"<p><strong>Objectives: </strong>To generate current reference values for height velocity (HV, cm/year) in German children and adolescents and to evaluate the sensitivity of auxological parameters in the evaluation of short stature (referral criteria).</p><p><strong>Methods: </strong>The study population consisted of healthy German participants of the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study (1985-2022). In total, data was available from n=453 girls (mean age 9.1 ± 2.4 years) and n=473 boys (mean age of 9.6 ± 2.5 years). As the participants were measured repeatedly, 4,557 HV assessments for girls and 5,224 HV assessments for boys were analyzed (median number of observations in female was nine and in male 11). The reference percentiles were created using the LMS method. The referral criteria of the German Society for Pediatric and Adolescent Endocrinology and Diabetology (DGPAED) and of the Growth Hormone Research Society (GHRS) for further endocrinological evaluation were evaluated in a subsample.</p><p><strong>Results: </strong>The specificity of the referral criteria \"HV<25th centile for 1 year\" (DGPAED) was 10.4 % in girls and 4.3 % in boys. When this criterion was changed to \"HV<3rd centile for 1 year\" the specificity increased to 75.5 % in girls and 76.1 % in boys. With omission of the 5th criterion (\"height> -2.0 SD AND HV< -2.0 over 1 year\") of the six referral criteria of the GHRS, the specificity of the remaining five referral criteria was 91.4 % in girls and 90.5 % in boys.</p><p><strong>Conclusions: </strong>New reference centiles for HV are presented. With modification of the already proposed GHRS criteria, the specificity of the assessment of HV in the evaluation of short stature could be increased significantly.</p>","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}