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Journal of Pediatric Endocrinology and Metabolism

Official Journal of the German Society for Pediatric and Adolescent Endocrinology and Diabetology (DGPAED)

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Language: English

First published: January 1, 1985

Publication Frequency: 12 issues per year

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Objective
The Journal of Pediatric Endocrinology and Metabolism (JPEM) is a peer-reviewed journal that publishes cutting-edge articles on clinical investigations in pediatric endocrinology, diabetes, inherited metabolic disorders, metabolism and translational research. JPEM is an international journal devoted exclusively to endocrinology in the neonatal, pediatric and adolescent age groups. JPEM is a high-quality journal dedicated to pediatric endocrinology, diabetes and metabolic diseases in its broadest sense, including research on epidemiology, pathophysiology, multidisciplinary management and technology, filling a gap at a time of rapid expansion in the field.
JPEM is a hybrid journal published monthly in print and online. All contributions submitted for publication in JPEM are subject to single-anonymized peer review by at least two experts in the field, selected and invited by the Editor-in-Chief and a dedicated Editorial Team. JPEM publishes only English-language articles.
JPEM is the official journal of the German Society for Pediatric and Adolescent Endocrinology and Diabetology (DGPAED).

BEST PAPER AWARD
From 2025, the DGPAED and the publisher will jointly award a Best Paper Award for the best paper by a DGPAED member published in the Journal of Pediatric Endocrinology and Metabolism. The prize is endowed with 1000 euros and will be awarded at the 2nd JA-PED. The selection will be made by Prof. Clemens Kamrath, JPEM Editor-in-Chief, Prof. Annette Richter-Unruh and Dr. Sebastian Kummer, JPEM Asociate Editors. Submission deadline is October 1, 2025.
We look forward to receiving your submissions´at https://mc.manuscriptcentral.com/jpem

Topics
Pediatric Endocrinology // Pediatric Diabetes // Pediatric Obesity // Inherited Metabolic Diseases // Neonates/Neonatal Screening // Hormonal Disorders and Therapy // Adrenal Disorders // Pituitary Disorders // Thyroid Disorders // Disorders of Bone, Calcium and Vitamin D Metabolism // Growth Disorders // Endocrine Cancers // Disorders of Gonads and Puberty // Disorders of Sex Differentiation, Gender Dysphoria // Psychosocial Aspects of Chronic Conditions in Pediatric Endocrinology and Diabetology // Multidisciplinary Care for Children and Their Families

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Original Article, Review Article, Mini Review, Opinion Paper, Perspectives, Editorial, Case Report, Case Report and Review of the Literature, Short Communication, Letter to the Editor and Reply, Guidelines and Recommendations, Congress Abstracts

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Report on the 2nd Conference of the German Society for Paediatric and Adolescent Endocrinology and Diabetology (DGPAED) in Leipzig/Halle, Saale 2025

April 14, 2026

Thomas Michael Kapellen, Alexandra Keller, Susann Weihrauch-Blueher

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Effect of androgens on retinal microvasculature in prepubertal girls with isolated premature pubarche

April 14, 2026

Gamze Karataş, Derya Çepni Çakır, Aslı Kırmacı Kabakcı, Mehmet Egemen Karataş, Diğdem Bezen, Dilan Yıldız, Akın Çakır

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Objectives To evaluate the effect of androgens on retinal microvasculature in prepubertal girls with isolated premature pubarche (PP) with optical coherence tomography (OCT) and OCT angiography (OCTA). Methods Eighty-six prepubertal, non-obese girls with isolated PP with normal birth weight and 86 age-matched control girls were evaluated. Retinal microvascular structures in the macular and optic disc regions were examined using OCT and OCTA. Data from subjects with isolated PP were compared with data from healthy controls. Correlations between dehydroepiandrosterone sulfate (DHEA-S), androstenedione (AS), testosterone, 17-hydroxyprogesterone (17-OHP) levels, bone age, pubertal stage as well as OCT and OCTA parameters were evaluated. Results The inferior retinal nerve fiber layer (RNFL) thickness in the isolated PP group was significantly higher than the control group (p=0.007). A statistically significant increase in the vessel density (VD) was observed in temporal quadrant of the superficial capillary plexus (SCP) and inferior quadrant of the deep capillary plexus (DCP) in the isolated PP group compared with the control group (p<0.05). There were significant positive correlations between DHEAS, AS, testosterone levels and RNFL, macula-disk regions’s OCTA parameters (p<0.05). Conclusions In the isolated PP patients, thickening of RNFL and increased VD in the macula and optic disc region were recognized under the effect of androgens compared to the control group. In these patients, early microvascular changes can be detected noninvasively by means of OCT and OCTA. These findings suggest a potential link between androgen exposure and retinal microvascular alterations; however, further studies are needed to explore their clinical implications.
Open Access
Evaluation of male reproductive function after aromatase inhibitor treatment during adolescence: case series with literature review

April 14, 2026

Chengjun Dai, Jingchao Ding, Junrong Zhang, Jianfang Zhu, Yanlan Fang, Chunlin Wang

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Objectives Aromatase inhibitors (AIs) are widely used in clinical practice, including for the treatment of adolescents with short stature. However, their potential impact on the long-term reproductive function of male adolescents remains unclear. This exploratory study aimed to investigate this relationship. Methods We identified male patients with short stature who had completed AI therapy between 2015 and 2022 at the First Affiliated Hospital of Zhejiang University School of Medicine. A follow-up study was conducted in 2023 to assess semen parameters and retrospectively collect data on sex hormone levels and complications during the treatment period. Results Ten patients met the inclusion criteria and consented to participate. Of these, nine provided both semen and blood samples, while one provided only a blood sample. The median treatment duration was 1.93 years (range: 1.0–3.5 years), and the median age at treatment initiation was 12.7 years (range: 11–16 years). The median sperm concentration was 78.99 million/mL (range: 16.93–223.88 million/mL). The median acrosome integrity was 75.71 % (range: 30.9–93.4 %), and the median DNA fragmentation index (DFI) was 15.39 % (range: 8.62–25.72 %). Sex hormone levels for all patients were within normal ranges at follow-up, and the majority exhibited normal semen analysis results. Conclusions In this case series study, the administration of aromatase inhibitors during adolescence was not associated with adverse effects on reproductive function parameters in early adulthood. These preliminary findings do not raise concerns regarding long-term reproductive safety. But larger, prospective studies are warranted for confirmation.
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A novel multimorbidity: co-occurrence of neonatal diabetes mellitus and leukocyte adhesion deficiency type 1 in two siblings

April 13, 2026

Ilkyaz Turktan, Zehra Sule Haskologlu, Tugba Kontbay Cetin, Esin Figen Dogu, Elif Ozsu, Kamile Aydan Ikinciogulları, Zeynep Sıklar

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Objectives The coexistence of multiple genetic disorders in a single individual is more frequent in populations with high consanguinity rates. When a single diagnosis does not fully explain the clinical phenotype, the presence of additional genetic conditions should be considered. This approach is essential for accurate genetic counseling and optimal long-term management. Here, we aimed to present two siblings diagnosed with both neonatal diabetes mellitus (NDM) and leukocyte adhesion deficiency type 1 (LAD-1), a combination not previously reported. Case presentation We report two sisters born to consanguineous parents, both diagnosed with permanent neonatal diabetes mellitus and LAD-1. Genetic analysis revealed a homozygous c.-331C>G mutation in the INS promoter region and a homozygous c.388T>C mutation in the ITGB2 gene in both patients.The index case presented with hyperglycemia on the 14th postnatal day and was diagnosed with permanent NDM. She also had additional congenital anomalies, including meningomyelocele and developmental hip dislocation. Due to recurrent infections and decreased CD18 expression on leukocytes, she was subsequently diagnosed with LAD-1.The second sibling developed hyperglycemia on the second postnatal day and was diagnosed with permanent NDM. She also showed delayed umbilical cord separation, leukocytosis, and absent CD18 expression, leading to the diagnosis of LAD-1. Conclusions The coexistence of two distinct rare genetic disorders in the same individual is uncommon, and its occurrence in siblings is exceptionally rare. To our knowledge, the coexistence of LAD-1 and NDM has not been previously reported. These cases emphasize the importance of considering multiple genetic diagnoses in patients with atypical or complex clinical findings, especially in consanguineous populations. Early recognition is critical for appropriate clinical management and genetic counseling.
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Endocrine and metabolic features of PTEN hamartoma tumor syndrome in childhood: a pediatric case series

April 13, 2026

Nazlı Sultan Özsoy, Ahmet Baştürk, Derya Altay, Leyla Kara, Ülkü Gül Şiraz, Nihal Hatipoğlu

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Objectives Phosphatase and tensin homolog ( PTEN ) Hamartoma Tumor Syndrome (PHTS) is caused by germline inactivating mutations in the PTEN gene and is phenotypically variable, often presenting diagnostic challenges and systemic complications during childhood. Case presentation This case series presents four pediatric patients with confirmed PTEN mutations. The clinical features included juvenile polyposis, hypoglycemia, growth hormone deficiency, juvenile papillomatosis, thyroid nodules, cerebral cavernoma, and insulin resistance. Conclusions This report highlights the heterogeneous pediatric phenotype of PHTS and draws attention to the non-tumoral manifestations of PTEN mutations, including abnormalities in glucose metabolism, growth axis, and neurodevelopment. Early diagnosis and multidisciplinary follow-up are essential to prevent potential complications.
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The clinical picture of symptomatic Rathke cleft cysts in children

April 13, 2026

Ayse Nurcan Cebeci, Michaela Marx, Regina Trollmann, Michael Buchfelder, Helmuth G. Dörr, Joachim Woelfle

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A rare coexistence: tyrosinemia type III and Wolff–Parkinson–White syndrome

April 7, 2026

Emel Yılmaz-Gümüş, Emine Genç, Damla Kocaman, Berna Şaylan-Çevik, Hamza Polat, Esra Arslan-Ateş, Gözde Yazkan-Akgül, Sümeyye Sarıbaş-Akmehmet, Sebile Kılavuz, Burcu Öztürk-Hişmi

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Objectives Tyrosinemia type III is an extremely rare autosomal recessive disorder of tyrosine metabolism caused by mutations in the HPD gene, which encodes 4-hydroxyphenylpyruvate dioxygenase (HPPD). Wolff–Parkinson–White (WPW) syndrome is a congenital cardiac conduction disorder characterized by the presence of an accessory atrioventricular pathway. While each condition is rare in isolation, their coexistence has not been previously reported. Case presentation We present a unique case of a 6-year-old boy with known WPW syndrome who was admitted with ketotic hypoglycemia after prolonged fasting and omission of propranolol doses. Metabolic work-up revealed persistently elevated plasma tyrosine levels. Genetic testing confirmed tyrosinemia type III due to a novel homozygous HPD variant [c.559A>G (p.Asn187Asp)]. The persistence of the WPW pattern despite decreased plasma tyrosine levels suggests that there is no direct causal relationship. He was also diagnosed with attention-deficit/hyperactivity disorder, specific learning disorder, and borderline intellectual functioning. Conclusions This case highlights the importance of metabolic evaluation in pediatric patients presenting with unexplained hypoglycemia, particularly in the presence of pre-existing cardiac disorders.
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A case of Alström syndrome with growth hormone deficiency and dyslipidemia: a novel homozygous frameshift variant of ALMS1 c.5763del

April 7, 2026

Takeshi Goda, Hisakazu Nakajima, Yasuhiro Kawabe, Kitaro Kosaka, Toshiyuki Itoi, Yoko Kawai, Satoru Sugimoto, Tomoko Iehara

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Objectives Alström syndrome (AS, OMIM #203800) is a rare autosomal recessive disorder caused by biallelic pathogenic variants in ALMS1 , characterized by obesity, cardiomyopathy, retinal dystrophy, sensorineural hearing loss, and progressive hepatic and renal involvement. We report a pediatric case of AS complicated by growth hormone deficiency (GHD), focusing on the clinical course and potential metabolic effects of growth hormone (GH) replacement therapy. Case presentation A 13-year-old girl with AS presented with severe dyslipidemia, including hypertriglyceridemia (727 mg/dL), elevated total cholesterol (251 mg/dL), and low high-density lipoprotein cholesterol (23 mg/dL), together with dilated cardiomyopathy. She was diagnosed with GHD at 3 years of age, with a height of −3.6 SD. GH replacement therapy led to sustained improvement in linear growth, reaching −1.9 SD, and was associated with long-term maintenance of lipid parameters within the normal range. Whole-exome sequencing identified a previously unreported homozygous frameshift variant in ALMS1 (NM_001378454.1:c.5763del; p.(Phe1921Leufs*18)). Conclusions This case suggests that GH replacement therapy may contribute to improved lipid metabolism in patients with AS complicated by GHD. In addition, it expands the mutational spectrum of ALMS1 and highlights the potential metabolic benefits of early endocrine intervention in AS.
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Volumetric MRI assessment of brain and pituitary structure in girls with central precocious puberty

March 19, 2026

Safa Özyılmaz, Leyla Gizem Bolaç Özyılmaz, Deniz Çeliker, Fatma Dursun, Sevinç Taşar

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Objectives To compare global and regional brain volumes and pituitary morphology between girls with central precocious puberty (CPP) and age-matched controls using intracranial-volume (ICV)-adjusted magnetic resonance imaging (MRI), and to assess associations between gonadotropins and brain volumetry. Methods This retrospective study included 182 girls (CPP n=91; controls n=91; age 6–9 years at MRI acquisition). Brain MRI (1.5 T) was segmented using the volBrain pipeline, and global and regional volumes were normalized to ICV. Pituitary height and volume were measured by two blinded radiologists. Group differences were analyzed with Welch t -tests; ANCOVA was applied for age and ICV adjustment. Multiple comparisons were FDR-corrected. Correlations with basal and GnRH-stimulated LH were evaluated using Spearman analysis. Results CPP patients had more advanced pubertal staging, higher height SDS, and greater pituitary height, while pituitary volume was similar. Global intracranial and total brain volumes did not differ. The WM/ICV fraction was modestly lower in CPP, whereas GM/ICV and CSF/ICV fractions were comparable. No regional brain volumes remained significant after FDR correction. In the stimulation-test subgroup, higher peak LH correlated with smaller total-brain/ICV and cerebrum/ICV fractions and with greater CSF/ICV. Conclusions After adjusting for age and intracranial volume, CPP showed preserved global and regional brain structure. Modest WM reduction and LH-related shifts in brain–CSF distribution suggest subtle hormonally mediated differences in maturational timing. This study provides the largest ICV-normalized volumetric MRI dataset in CPP.
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46,XY differences of sex development in pontocerebellar hypoplasia type 7 (PCH7): two case reports and systematic review

March 19, 2026

Shaila Sanjay Pachapure, Akshay Kalavant B., Santosh B. Kurbet, Vijaya Sarathi

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Objectives We report two cases of 46,XY siblings with pontocerebellar hypoplasia type 7 (PCH7) and conduct a systematic literature review for genetically confirmed PCH7 cases, focusing on phenotypic characteristics, particularly gonadal parameters, and associated genotypic data. Case presentation Two 46,XY siblings diagnosed with PCH7 were reviewed. Both exhibited hypoplastic male external genitalia, absent uterus, and cryptorchid testes, confirmed through histological assessments showing dysgenesis. A systematic literature search revealed an additional 26 cases of 46,XY PCH7, with neurological involvement noted in all cases except one. The external genitalia were described as abnormal (17/23); however, few of these were hypoplastic male type on pictorial review. Nonlocalized testes (5/5) and absent uterus (4/7) on ultrasonography, elevated FSH (7/7), and low testosterone (3/3) were observed. Besides a novel variant (p.Ile133Thr) in Indian siblings, a total of 25 variants in TOE1 were identified with no specific genotype–phenotype correlation. Conclusions Testicular development was defective in all PCH7 patients but was variable, with the predominant phenotypic manifestation being testicular regression syndrome/partial gonadal dysgenesis with Müllerian duct regression (TRS/PGD-MDR).
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New insights into Oliver–McFarlane syndrome: adrenocortical hypofunction and variable expressivity in a Chinese sibling pair

March 19, 2026

Caiqi Du, Tingting Yu, Sheng Liu, Hao Fu, Aoyu Yang, Haotian Zhang, Yan Liang, Xiaoping Luo

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Objectives Oliver-McFarlane syndrome (OMS) is an extremely rare autosomal recessive disorder primarily characterized by the triad of trichomegaly, congenital hypopituitarism, and chorioretinal degeneration. This study aims to report the clinical and genetic characteristics of the first identified Chinese sibling pair with OMS and to expand the known phenotypic spectrum by documenting a novel clinical feature. Case presentation We report two Chinese siblings with OMS harboring identical compound heterozygous PNPLA6 variants: c.2990C>T (p.Ser997Leu) and c.3367G>A (p.Gly1123Arg). Both presented with growth hormone deficiency (GHD), short stature, retinitis pigmentosa, and characteristic hair anomalies. Notably, the elder brother exhibited intellectual disability and secondary adrenocortical insufficiency – a feature not previously documented in OMS. In contrast, the younger sister had normal adrenal function and higher cognitive levels. Both patients showed a significant positive growth response to recombinant human growth hormone (rhGH) therapy. Conclusions This study expands the phenotypic spectrum of PNPLA6 -associated OMS to include adrenocortical insufficiency and highlights significant intrafamilial variability.
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Family and culture in type 1 diabetes transition care: a mini review

March 19, 2026

Jennifer A. Kelleher, Megan Kozak, Hiroko Sugiwaka, Lindsay R. Druskin Grimes, Christina L. Duncan

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Transition readiness interventions support the health and independence of adolescents and young adults (AYAs) with type 1 diabetes (T1D) as they move from pediatric to adult healthcare. A theoretical model of transition readiness emphasizes the importance of family and culture in AYA disease management. Yet, it remains unclear how family and culture are currently incorporated into T1D transition readiness interventions and how such factors may support AYAs during this transition. This mini review summarizes the literature and its gaps regarding family and culture in T1D transition interventions to assist in the continued refinement of such interventions. Of the 524 articles reviewed, only 16 met inclusion criteria (e.g., about T1D transition readiness intervention, discusses family or cultural factors). Six (37.5 %) T1D transition interventions involved a family component alone, four (25 %) incorporated cultural components alone, and six (37.5 %) included both a cultural and a family component. The level of caregiver involvement in these interventions ranged from none to caregiver-specific materials or education. Although culture was considered in multiple interventions, only one directly addressed family/cultural values. Future interventions should consider how to adapt transition readiness interventions to AYA and familial cultural beliefs, thereby optimizing AYA diabetes self-management behaviors and independence during transition to adult care.
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Bone age advancement in non-obese children with premature adrenarche: relationship to growth acceleration and predicted adult height outcomes

March 17, 2026

Nurdan Çiftci, Abdulgani Gülyüz

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Objectives Premature adrenarche (PA) is commonly associated with bone age (BA) acceleration, but it is difficult to assess the independent contribution of adrenal androgens to skeletal maturation in studies that include obese children. This study examined BA advancement in non-obese children with PA and evaluated predicted adult height (PAH) estimates in this population. Methods The medical records of children diagnosed with PA between April 2022 and April 2023 were reviewed retrospectively. Children who were obese, had congenital adrenal hyperplasia, central precocious puberty, genetic or syndromic disorders affecting growth, or were small for their gestational age were excluded. Anthropometric, hormonal, and radiological data were collected. BA was assessed using the Greulich–Pyle standards, and PAH was calculated using the Bayley–Pinneau method. Analyses were designed to evaluate associations rather than causal relationships. Results Eighty-four non-obese children with PA (85.7 % female; mean age 7.41 ± 0.67 years) were included. The mean BA–CA difference was 0.59 ± 0.96 years. Children with a BA–CA difference of ≥1 year had significantly higher height SDS and BA (p<0.001), whereas serum DHEA-S levels did not differ across BA–CA groups. BA–CA was positively associated with height SDS and negatively associated with PAH SDS relative to current height SDS. In multivariable analyses, height SDS showed an independent association with BA advancement, whereas serum DHEA-S did not. Conclusions In non-obese children with PA, BA advancement appears to be more closely associated with linear growth status than with circulating DHEA-S concentrations within the constraints of this study design. In most patients, predicted adult height remained within the genetic target range; however, approximately 20 % had PAH values below their mid-parental height. Longitudinal studies incorporating final adult height measurements and comprehensive hormonal profiling are required to clarify long-term growth outcomes.
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Association of MC4R rs17782313 and multi-locus genetic variants with metabolic syndrome in Northern Vietnamese children aged 6–11 years: an exploratory study

March 17, 2026

Thi Hong Hanh Nguyen, Quang Binh Tran, Thi Nhung Bui, Thi Anh Dao Duong, Thi Tuyet Le

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Objectives Metabolic syndrome (MetS) is a multifactorial disorder associated with increased cardiometabolic risk. This exploratory study aimed to investigate the associations between five candidate single nucleotide polymorphisms (SNPs) and their haplotypes with MetS in children aged 6–11 years from Northern Vietnam. Methods A total of 547 children aged 6–11 years were included, comprising 39 children with MetS and 508 controls. MetS was defined using age-specific criteria based on modified International Diabetes Federation and National Cholesterol Education Program definitions. Genotyping of APOE -rs429358, APOE -rs7412, FTO -rs6499640, MC4R -rs17782313, and TMEM18 -rs6548238 was performed using polymerase chain reaction–restriction fragment length polymorphism analysis. Multivariable logistic regression adjusted for age, sex, and region was applied. Results MC4R -rs17782313 showed a significant associated with MetS. Under the recessive model, the C/C genotype was associated with increased MetS likelihood after adjustment (OR=2.28, p=0.005). A log-additive association was also observed (OR=2.03, p=0.014). No significant associations were detected for the other SNPs. Haplotype analysis suggested that three five-locus combinations were associated with higher MetS risk compared with the most common haplotype (T–C–G–T–C) (all p<0.05). Conclusions These findings suggest that MC4R rs17782313 may contribute to MetS susceptibility in this population. Given the limited number of MetS cases, results should be interpreted cautiously and require validation in larger pediatric cohorts and mechanistic studies.
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The prevalence of autoimmune diseases in antibody negative type 1 diabetes mellitus

March 16, 2026

Shadi Bakjaji, Amit Lahoti, Robert P. Hoffman, Leena Mamilly

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Objectives Type 1 diabetes mellitus (T1D) results from autoimmune destruction of pancreatic β cells. T1D individuals face increased risk of autoimmune thyroid disease (AITD) and celiac disease (CD). While most patients present with β-cell autoantibodies, 5–10 % do not and are classified as antibody-negative T1D (AB− T1D). Whether autoimmune disease risk differs between AB− and antibody-positive T1D (AB+ T1D) remains uncertain. Methods Children aged 6 months to 18 years diagnosed with T1D between January 2010 and June 2023 were reviewed and categorized as AB+ or AB− based on islet cell antigen, insulin, and GAD-65 autoantibodies at diagnosis. Each AB− patient was matched with two age- and sex-matched AB+ controls within the diagnosis date. Chi-square testing compared CD and AITD prevalence between groups, with significance set p<0.05. Results The study included 149 AB− and 298 AB+ subjects. CD prevalence was 5.0 % in the AB+ group and 3.4 % in the AB− group. AITD prevalence was 4.4 % in the AB+ group and 2.7 % in the AB− group. No significant differences were identified. A combined diagnosis of CD and AITD occurred only in the AB+ group (2.2 %, p=0.024). At diagnosis, AB+ patients had higher glucose and beta-hydroxybutyrate levels and lower C-peptide, while venous pH was similar. Conclusions AITD and CD prevalence did not differ significantly between AB− and AB+ children with T1D, though coexistence of both conditions occurred only in AB+ patients. These findings suggest that AB− T1D may still involve autoimmunity and support similar surveillance strategies for autoimmune diseases in both groups.
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LRP5-related primary osteoporosis: phenotypic spectrum and treatment response to zoledronic acid

March 16, 2026

Chamila Balagamage, Proteek Sen, Nicola Crabtree, Denise Williams, Suma Uday

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Objectives Lipoprotein receptor–related protein-5 ( LRP5 )-related disorders are characterized by variably reduced vision and juvenile osteoporosis due to loss-of-function mutations in the low-density LRP5 gene. Compelling evidence on effectiveness of bisphosphonate treatment in these disorders remains limited. We aimed to describe the phenotypic spectrum and clinical, densitometric, and fracture outcomes following zoledronate therapy in children with LRP 5-related disorders. Case presentation Five patients (P1–P5), referred at a median age of 9 years for recurrent low-impact fractures with confirmed LRP5 mutations, were included. P1–P3 were siblings with a homozygous c.1259 G>Cp.(Gly420Ala), variant of likely pathogenic. P4 carried compound heterozygous mutations for three sequence variants, including novel pathogenic variants c.2449 C>T p.(Arg817Cys), and c.362A>Gp.(Lys121Arg), and P5 had a heterozygous c.4502C>Tp.(Pro1501Leu) variant, also identified in the mother, a variant of uncertain significance (VUS). Four patients (P2–P5) received zoledronate for a median duration of 2 years (range 1.5–11 years). Post-treatment, P2, P3, and P5 showed improvements in lumbar spine (LS) Bone Mineral Apparent Density (BMAD) Z-scores (+1.0, +0.7, and +2.7 respectively), remaining fracture-free. P4 exhibited an increase in LS BMAD (+0.3) and vertebral remodeling. Conclusions LRP 5-related disorders should be considered in patients with recurrent fractures and visual involvement. Zoledronate appears effective in improving bone density, reducing fracture frequency, and promoting vertebral remodeling, although further studies are required to determine optimal treatment duration.
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GATA4 gene variants in 46,XY differences of sex development: report of four cases and literature review

March 16, 2026

Maria Mansó Borràs, Cristina Pellicer Viudes, Carmen De Mingo Alemany, Sara León Cariñena, Teresa Jaijo Sanchis, Francisca Moreno Macián

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Objectives 46,XY differences of sex development (DSD) comprise a heterogeneous group of congenital conditions affecting chromosomal, gonadal or anatomical sex differentiation. GATA4 is essential for cardiac and gonadal development, although its role in DSD is not fully understood. We report four 46,XY DSD cases with GATA4 variants from our center and performed a literature review. Case presentation Case 1 presented with ambiguous genitalia, persistent Müllerian structures, and complex congenital heart disease; a GATA4 variant (p.Cys239Arg) was identified, and gonadectomy revealed atrophic testes. Case 2 had penoscrotal hypospadias and a ventricular septal defect, carrying a synonymous GATA4 variant (p.Cys275=) and showing normal hormonal evaluation and pubertal development. Case 3 presented with perineal hypospadias and a GATA4 variant (p.Val305Ile), along with a maternally inherited RET mutation; his twin brother, carrying the same variants, had no DSD. Both exhibited spontaneous puberty. Case 4 presented with isolated hypospadias and a GATA4 variant (p.Arg261GLn) without cardiac anomalies. Conclusions GATA4 should be included in genetic panels for 46,XY DSD. Our work expand the clinical and molecular spectrum of GATA 4 -associated 46,XY DSD and our review support the relevance of zinc finger domain variants in gonadal development. Phenotypic variability among carriers supports variable expressivity and incomplete penetrance.
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Long-term outcomes in ovotesticular DSD: insights from a single-centre Indian cohort

March 16, 2026

Niragi Mehta, Anurag Lila, Anuj Ban, Manjiri Karlekar, Saba Samad Memon, Rohit Barnabas, Vijaya Sarathi, Nalini Shah, Tushar Bandgar

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Objectives Ovotesticular disorders of sex development (OT-DSD) are rare disorders that constitute ∼5 % of all DSDs. Data on long-term outcomes with respect to gender identity, gonadal malignancy, pubertal/adulthood gonadal and sexual functions are scarce. Methods This retrospective study, reports the long-term outcomes of patients with OT-DSD from a single centre in western India. Results Fifteen patients (14: 46XX, 1: 46XX/46XY) with atypical genitalia and diagnosed as OT-DSD (unilateral-OT with contralateral ovary: 8, bilateral-OT: 3, lateral gonads: 4) were followed up for a median duration of 8.25 (2.1–28) years. 14/15 patients underwent gonadectomy (bilateral in 4). Sex of rearing was male in 14, and none reported gender incongruence/dysphoria. Nine adult males had varied concerns, including gynecomastia (n=9), periodic hematuria (n=3), periodic abdominal pain (n=3), acute abdomen (n=1), hypogonadism requiring testosterone replacement (n=8), genitoplasty-related complications (n=3; urethral fistula in one and poor urine stream requiring intermittent catheterisation in two), short stature [median final height SDS: −2.3 (−3.0 to −0.5)]. Two males reported having sexual relationships. Overall gonadal malignancy rate was 6.6 % (1/15), it was seen in the only patient raised as female (46, XX) who presented at 20.7 years with a right adnexal mass (dysgerminoma from the ovotestes) and primary amenorrhoea. She underwent right gonadectomy and is currently on estrogen and progesterone replacement. Conclusions Majority of patients with OT-DSD were reared as males and had a male gender identity, most had short final height and adulthood hypogonadism. Although the risk of gonadal malignancy is low, it cannot be ruled out even in 46XX karyotype. These observations will help in counselling families with affected members.
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A rare case of severe short stature diagnosed after late-onset hypocalcemia: Kenny–Caffey syndrome type 2

March 16, 2026

Gülşen Özer, İbrahim Mert Erbaş, Durdugül Ayyıldız Emecen, Akçahan Akalın, Tarık Kırkgöz, Özge Köprülü, Özlem Nalbantoğlu, Filiz Hazan, Behzat Özkan

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Objectives Kenny–Caffey syndrome type 2 (KCS2) is a very rare genetic disorder characterized by growth retardation and hypoparathyroidism, due to autosomal dominantly inherited pathogenic variants in the FAM111A gene. In this report, we presented a pediatric patient diagnosed as KCS2, with severe short stature and late-onset hypocalcemia. Case presentation A 7-year-old male patient was referred to our clinic for growth retardation. His body weight, height, and body mass index were 13.1 kg [(−4.9) standard deviation (SD) score], 94.8 cm (−5.4 SD score), and 14.6 kg/m 2 (−0.8 SD score), respectively. He had dysmorphic features including a triangular face, frontal bossing, low-set ears, and a bulbous nose. His height velocity was 3.97 cm/year (−1.1 SD score), and serum insulin-like growth factor-1 level was low. The peak growth hormone (GH) response during the GH stimulation tests was 8.5 ng/mL. Pituitary magnetic resonance imaging showed a partially empty sella and GH treatment was initiated. At the end of the first year of treatment, routine laboratory tests revealed hypocalcemia, hyperphosphatemia, and inappropriately low parathyroid hormone levels. His skeletal survey demonstrated cortical thickening and medullary stenosis of the long bones. Based on these findings, KCS2 was considered in the differential diagnosis, and genetic testing revealed a heterozygous pathogenic variant (c.1706G>A) in FAM111A . Conclusions KCS2 should be considered in patients with severe growth retardation and hypoparathyroidism, particularly when cortical thickening and medullary narrowing of long bones are observed. Responses to the GH treatment may vary among those individuals, and hypocalcemia may occur in the form of transient episodes.
Open Access
Pediatric thyroid cancer lung metastases and RAI: long-term results

March 16, 2026

Ryan C. Mueller, Nikhil Rammohan, Anthony J. Apicelli, Ana Maria Arbelaez, Farrokh Dehdashti, Barry A. Siegel, Vikas Prasad, Perry W. Grigsby, Stephanie Markovina

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Objectives Children with differentiated thyroid cancer (DTC) often present with lung metastases but historically have good outcomes. Radioactive iodine (RAI) is commonly used to treat these children. Given the rarity of this condition, little evidence detailing long-term outcomes and risk of radiation pneumonitis exists. Methods We conducted a retrospective analysis of patients <20 years old who received RAI for DTC lung metastases between 1973 and 2018. Disease-free survival (DFS) was calculated from diagnosis to last follow-up. Overall survival and rates of acute and late radiation pneumonitis were determined by chart review and obituary searches. Results Sixteen patients met eligibility criteria. Fourteen presented with thyroid, nodal, and lung disease; one presented with thyroid and nodal disease with nodal and lung recurrence; and one presented with thyroid-only disease with nodal and lung recurrence. All patients underwent thyroidectomy, 10 underwent neck dissection, and four underwent lymph node excision. Median per-treatment and cumulative RAI dose were 100 mCi (20–270 mCi) and 340 mCi (25–970 mCi), respectively. Median follow-up was 13 years (1–32 years). Fifteen patients (88.2 %) were alive at last follow-up. Twelve had no evidence of disease, two had improved but persistent I-131 uptake within lungs and surgical bed, and one had improved but persistent lung metastases alone. No evidence of symptomatic radiation pneumonitis was evident in the medical records of these patients. Conclusions Patients <20 with DTC lung metastases have high survival following thyroidectomy and RAI treatment and apparently low rates of radiation pneumonitis despite high cumulative doses.
Open Access
Pituitary dysfunction in childhood after [¹⁷⁷Lu]Lu-DOTATATE therapy

March 6, 2026

Karen van Wessel, Bart de Keizer, Miranda P. Dierselhuis, Max M. van Noesel, Hanneke M. van Santen

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Objectives Treatment for neuroblastoma with chemotherapy and [ 131 I]MIBG can induce endocrine adverse effects, including thyroid disorders, gonadal insufficiency or short stature. Neuroblastoma can also be targeted at the somatostatin receptor, using [ 177 Lu]Lu-DOTATATE peptide receptor radionuclide therapy. Thus far no endocrine effects have been reported after [ 177 Lu]Lu-DOTATATE treatment in children. Case presentation We report a first case of pituitary dysfunction, reflected as growth hormone deficiency and central hypothyroidism, following treatment with [ 177 Lu]Lu-DOTATATE for refractory neuroblastoma. Conclusions We hypothesize that the GH and TSH deficiency in this case are caused by pituitary damage through binding of [ 177 Lu]Lu-DOTATATE to the somatostatin receptors in the pituitary gland. If [ 177 Lu]Lu-DOTATATE in the future becomes a more upfront treatment we strongly underline screening on pituitary dysfunction after exposure to [ 177 Lu]Lu-DOTATATE in childhood.
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Challenges of pediatric ectopic ACTH syndrome from sacrococcygeal teratoma

February 26, 2026

Ruochen Che, Jianfeng Zhou, Chunlei Zhou, Jingnan Gao, Guoqiang Shao, Tao Li, Yuan Han

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Objectives Ectopic ACTH syndrome (EAS) is a rare cause of Cushing’s syndrome, especially in children, and has been only exceptionally linked to sacrococcygeal teratomas (SCTs). We report a pediatric case of SCT-associated EAS and review the literature to highlight diagnostic challenges and management strategies. Case presentation A 13-year-old girl presented with hypertension, hypokalemia, hyperglycemia, and rapid weight gain. Biochemical testing confirmed ACTH-dependent hypercortisolism, while pituitary MRI was negative. Pelvic CT revealed a 5.1 cm presacral mass. PET/CT based on ^18F-FDG showed only mild glucose uptake (SUVmax 3.26) in the mass, whereas ^68Ga-DOTA-NOC PET/CT demonstrated intense somatostatin receptor (SSTR) expression (SUVmax 55.86). Laparoscopic resection identified a mature teratoma containing a well-differentiated neuroendocrine tumor (NET G1) positive for ACTH and SSTR2. Postoperatively, cortisol/ACTH levels normalized, and metabolic abnormalities resolved with 9-month follow-up showing no recurrence. Conclusions This report describes the first adolescent case of EAS due to a neuroendocrine tumor within a sacrococcygeal teratoma. Complementary PET/CT on FDG metabolism and SSTR expression is critical for localizing occult neuroendocrine components. Complete tumor resection and multidisciplinary collaboration are key to favorable outcomes, expanding the spectrum of pediatric EAS and providing valuable insight into its evaluation and management.
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Hypertrophic cardiomyopathy as a novel phenotypic feature of NSUN3-related mitochondrial disease: a case report with review of the literature

February 24, 2026

Ayşe Şenol Ersak, Tuğçe Çağıran, Ayşen Koçyiğit, Kısmet Çıkı, Yılmaz Yıldız, Ebru Aypar, Serap Ketenci İşlek, Pelin Özlem Şimşek Kiper, Göknur Haliloğlu, Ali Dursun

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Objectives NSUN3 encodes a mitochondrial RNA methyltransferase responsible for cytosine methylation at the tRNA wobble base, which plays a role in the regulation of mitochondrial translation. Variants in NSUN3 lead to impaired oxidative phosphorylation resulting in multisystem involvement. Reported cases to date have described developmental delay, hypotonia, optic atrophy and neurological involvement. Cardiac manifestations, however, have not yet been clearly associated with NSUN3 deficiency. Here, we report hypertrophic cardiomyopathy (HCM) as a new clinical feature and the long-term follow-up of our case, further expanding the phenotype of NSUN3 -related disease. Case presentation An 18-year-old girl was referred for visual loss, progressive fatigue, muscle weakness and HCM. Initial symptoms started as hypotonia in infancy and proceeded with developmental delay, reduced visual acuity and chest pain. At the age 15 years, she was diagnosed with HCM. Cardiac magnetic resonance imaging showed concentric left ventricular (LV) hypertrophy with septal thickness measuring up to 20 mm, LV ejection fraction was preserved (70 %). Whole exome sequencing identified a homozygous likely pathogenic variant in the NSUN3 gene: NM_022072.5: c.465dup (p.Gly156ArgfsTer6), for which both parents were found to be heterozygous carriers. Conclusions To our knowledge, this is the first reported case of NSUN3 -related mitochondrial disease with HCM. An increasing number of reported cases will likely contribute to a more comprehensive understanding of the clinical phenotype and genotype–phenotype correlations.
Open Access
Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED): a case series and experience from a UK tertiary paediatric hospital

February 20, 2026

Alaa Baioumi, Karthik Darma, Lakshmi Selvarajan, Rachel Hamblin, Sarah Armstrong, Michal S. Lionakis, Marion Roderick, Toby Candler

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Objectives Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a multi-system autoimmune disorder caused by AIRE gene variants. Diagnosis can be challenging and often delayed. A specialised clinic for children and young people with APECED established in 2024 at Bristol Royal Hospital for Children, recruited patients from South-West England. We describe the diagnostic journey, disease progression and management challenges for 4 patients with APECED. Case presentation All cases had a history of fungal nail infections and chronic mucocutaneous candidiasis preceding the development of endocrinopathy. Hypoparathyroidism was the most common endocrine presentation (n=3). Two patients had pancreatic exocrine dysfunction requiring pancreatic enzyme replacement. One patient had primary ovarian insufficiency (POI) aged 11. One female without evidence of POI was referred to fertility services to discuss fertility preservation. Immunomodulation was used in 2 patients; 1 received sirolimus, rituximab, corticosteroids, mycophenolate followed by ruxolitinib and 1 patient recently started ruxolitinib. Conclusions Inter-speciality working is important to detect and manage a range of comorbidities as new immunomodulatory therapies that aim to prevent disease progression are emerging. Proactive screening for certain autoantibodies such as 21-OH can help predict patients at risk of certain endocrinopathies and may provide an opportunity for early intervention to prevent long-term morbidity.
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A novel CEP57 gene mutation in mosaic variegated aneuploidy syndrome 2: case report

February 16, 2026

Cristina Pellicer Viudes, María Mansó Borrás, Susana Enrique Madrid, Berta Diago García, Armando Carlos Maruenda Jiménez, Paula Guzmán Tena, María Leticia Vázquez Álvarez, Victoria Cañadas Olmo, Dolores Tío Guillamón, María Amparo Edo Tena, Edurne Novella-Maestre, Purificación Marín Reina

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Objectives Mosaic variegated aneuploidy syndrome 2 (MVA2) is an uncommon autosomal recessive genetic condition caused by mutations in the CEP57 gene. It is characterized by intrauterine growth restriction, severe short stature, facial dysmorphism, and skeletal abnormalities. Most affected individuals also show congenital cardiac defects and delayed development. To date, only 16 patients have been reported. Case presentation We report a 6-year-old girl of consanguineous Moroccan parents, presenting with severe short stature, clinodactyly, and dysmorphic facial features including prominent forehead, triangular face, micro-retrognathia, and low set ears. Neurodevelopment was initially normal, but mild intellectual disability was then noted. Genetic testing including karyotype, array-CGH, and Silver–Russell syndrome were normal. Finally, whole exome sequencing revealed a homozygous c.834_844dupCAATGTTCAGC variant in CEP57 , classified as likely pathogenic. Familial segregation confirmed heterozygosity in both parents and siblings. Conclusions This report describes a novel homozygous variant of CEP57 , expanding the clinical and genetic spectrum of MVA2 syndrome. Although, karyotype should be firstly requested if MVA is suspected, whole exome sequencing is crucial. Growth hormone therapy shows limited response in this syndrome, and the association with cancer predisposition should be further studied.
Open Access
Childhood thiamine-responsive megaloblastic anemia and diabetes: a case series highlighting early diagnosis and management

February 3, 2026

Uğur Cem Yılmaz, Arpita Bhriguvanshi, Deniz Özalp Kızılay, Samim Özen, Şükran Darcan, Yusuf Can Doğan, Esra Işık, Nihal Karadaş, Jamie R. Wood, Ingrid Libman, Damla Gökşen

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Objectives Thiamine-responsive megaloblastic anemia (TRMA) is a rare but clinically impactful disorder caused by pathogenic SLC19A2 variants. Despite its characteristic triad – megaloblastic anemia, non-autoimmune early-onset diabetes, and sensorineural hearing loss – TRMA is frequently unrecognized at initial presentation, delaying life-altering treatment. This report highlights how early thiamine therapy can rapidly reverse dysglycemia and hematologic abnormalities, and how diagnostic delay may permit irreversible neurological injury. Case presentation Case 1, a six-month-old male, presented with diabetic ketoacidosis and profound anemia. High-dose thiamine produced a striking metabolic response: near-immediate glycemic stabilization, complete insulin discontinuation within days, and normalization of hematologic parameters. Despite optimal early treatment, progressive hearing loss necessitated cochlear implantation. Case 2, a three-year-old male, exhibited recurrent anemia, difficult-to-control diabetes despite insulin therapy, and established sensorineural hearing impairment, following a stroke at age two. Thiamine initiation after delayed genetic confirmation improved dysglycemia and corrected anemia, yet neurological sequelae remained fixed. Conclusions These cases underscore TRMA as a high-impact, reversible cause of early-onset diabetes – but only when recognized promptly. Thiamine can induce complete metabolic remission and insulin independence, offering a therapeutic opportunity unmatched in most pediatric diabetes etiologies. However, once neurological damage develops, metabolic correction alone is insufficient. TRMA should be urgently considered in any child with recurrent macro/megaloblastic anemia and atypical or antibody-negative diabetes, especially with hearing concerns. Early genetic testing and immediate thiamine therapy are essential to prevent avoidable, lifelong morbidity. In children with unexplained megaloblastic anemia and atypical diabetes, immediate TRMA screening may prevent irreversible complications.
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Meier–Gorlin syndrome due to a recurrent DONSON variant in a Turkish family: first report of thumb aplasia and long-term growth data

February 2, 2026

Abdullah Sezer, Fatma Zehra Yalçın, Abdulkerim Kolkıran, Semra Çetinkaya

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Objectives Meier–Gorlin syndrome (MGORS) is a rare primordial dwarfism characterized by microtia, patellar hypoplasia/aplasia, and short stature. Additional features may include skeletal, respiratory, urogenital, and endocrine abnormalities. 13 genes have been implicated, with DONSON , essential for replication fork stability and intra–S phase checkpoint activation, being the most recently identified. Only six patients with DONSON -related MGORS have been reported. This study expands the phenotype by presenting long-term follow-up and prenatal data in two affected siblings. Case presentation The index patient, a 10-year-old male, had short stature, microcephaly, microtia, craniofacial features, hearing loss, patellar aplasia, and genitourinary anomalies. Despite an early growth delay, his height progressively improved without intervention. Whole-exome sequencing revealed a homozygous pathogenic c.631C>T p.(Arg211Cys) variant in DONSON (NM_017613.3). Following genetic counseling, the family declined prenatal testing in a subsequent pregnancy complicated by intrauterine growth restriction. The newborn female sibling carried the same variant and displayed DONSON -related MGORS features, including the first reported case of thumb aplasia. Additional findings in the family included renal hypoplasia, 2–4 toe syndactyly, and hypospadias. Conclusions This is the third report of DONSON c.631C>T p.(Arg211Cys) in Turkish patients. While the recurrence in the same population suggests a founder effect, haplotype–based analysis is required. Thumb aplasia expands the known phenotype of DONSON -related MGORS, and the observed moderate course of growth retardation offers prognostic value. These findings highlight the importance of including DONSON in MGORS gene panels, considering population-specific variants, and systematically documenting rare phenotypic features to improve diagnosis, follow-up, and genetic counseling.
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Berardinelli–Seip congenital lipodystrophy type-2: a case series of three Indian children

February 2, 2026

Surbhi Gyani, Mithila Das Mazumder, Medha Mittal, Swati Dokania, Anuradha Rai, Prabhakar Bindhu, Seema Kapoor

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Objectives Congenital generalised lipodystrophies (CGL) are a group of rare genetic disorders characterised by absence of adipose tissue and disturbances in lipid and carbohydrate metabolism. These disorders are characterised by distinct muscular phenotype with acromegaloid features, acanthosis nigricans and hepatomegaly. Metabolic disturbances lead to long-term complications such as diabetes, metabolic fatty liver disease, pancreatitis and cardiovascular disease. To highlight the clinical features and diagnostic approach towards lipodystrophies through the presentation of three Indian children with classical phenotypic and biochemical features. Case presentation Three Indian children (two siblings and one unrelated child), all born to non-consanguineous parents with uneventful perinatal histories, presented with progressive abdominal distension and developmental delay. Clinical examination showed generalised loss of subcutaneous fat, muscular habitus, acanthosis nigricans, and hepatosplenomegaly. Laboratory investigations revealed elevated transaminases and hypertriglyceridaemia. Ultrasonography showed hepatomegaly with fatty liver changes. Exome sequencing confirmed presence of variants consistent with the diagnosis of CGL. Though metreleptin was not available, diet modification and increased physical activity were initiated along with lipid lowering drugs which have helped to improve the dyslipidaemia in the siblings. Conclusions CGL is a rare but distinct disorder that should be considered in children presenting with generalised muscularity, hepatomegaly, and metabolic abnormalities.
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Successful desensitization to alglucosidase alfa in a very young infant with Pompe disease

January 20, 2026

Funda Aytekin Güvenir, Gökhan Yörüsün, Zeynep Şengül Emeksiz, Oya Kıreker Köylü, Aynur Küçükçongar Yavaş, Emine Dibek Mısırlıoğlu

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Objectives Enzyme replacement therapy (ERT) with alglucosidase alfa markedly improves outcomes in infantile-onset Pompe disease, yet hypersensitivity reactions may interrupt treatment and require desensitization. We report a very young infant in whom ERT was successfully maintained after allergic reactions through a structured desensitization protocol. Case presentation A 3-month-old male with infantile-onset Pompe disease developed generalized urticaria during the seventh alglucosidase alfa infusion despite premedication and infusion rate adjustment. Skin testing was not feasible due to age. After obtaining informed consent, desensitization was initiated in a specialized setting. Initial three- and four-bag protocols were unsuccessful because of recurrent urticaria. A final five-bag, sixteen-dose protocol using enzyme concentrations from 0.0005 to 1 mg/mL enabled the full therapeutic dose to be administered safely. The same regimen was subsequently applied in following infusions without recurrence of symptoms. Conclusions This case demonstrates that desensitization can be effectively implemented even in very young infants with Pompe disease who experience hypersensitivity during ERT. A carefully designed protocol and close clinical monitoring allow continuation of this life-saving therapy when no alternative treatment exists.
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Dyggve–Melchior–Clausen syndrome in three siblings: a unique case series with dual diagnosis of Down syndrome and Hirschsprung disease

January 20, 2026

Meryem Halis, Mehmet Kocabey, Fatma Ceren Sarıoğlu, Suzan Süncak, Merve Bilen, Nur Arslan, Semra Gürsoy, Handan Güleryüz Uçar, Ayfer Ülgenalp, Özlem Giray Bozkaya

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Objectives Dyggve–Melchior–Clausen (DMC) syndrome is a rare autosomal recessive skeletal dysplasia caused by mutations in the DYM gene. It is characterized by progressive spondyloepimetaphyseal dysplasia, short stature, coarse facial features, microcephaly and intellectual disability. While it clinically resembles Morquio syndrome (mucopolysaccharidosis type IV, MPS IV), DMC is distinguished by cognitive impairment, absence of corneal clouding, normal urinary glycosaminoglycans and distinctive radiological features. Case presentation We reported three siblings with DMC syndrome. Two 4-year-old monozygotic male twins, born to consanguineous parents, presented with growth retardation and developmental delay. Radiographs showed generalized platyspondyly, rhizomelic shortening and metaphyseal dysplasia, while biochemical tests excluded MPS IV. Molecular tests revealed a homozygous deletion in exon 16 of the DYM gene. The third sibling, with Down syndrome, also exhibited similar skeletal features and carried the same DYM deletion. Conclusions The clinical and radiological features of our patients were consistent with DMC syndrome, with partial overlap with MPS IV. This case series represents the first reported coexistence of DMC and Down syndrome. In addition, we identified a novel homozygous deletion in exon 16 of the DYM gene, which broadens the known mutational spectrum. This finding also highlights the importance of comprehensive genetic testing when standard sequencing results are inconclusive. The presence of neurological findings, such as seizures, further supports the need for combined genetic and neurological evaluation in these patients.
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Severe metabolic acidosis in succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency: case report of a novel pathogenic OXCT1 variant (L131_E132dup) and its pathophysiological basis

January 13, 2026

Natsuho Adachi, Hideki Matsumoto, Mai Mori, Hideo Sasai, Hiroyuki Tanaka

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Objectives Ketoacidosis from idiopathic ketotic hypoglycemia (IKH) rarely causes severe acidemia or requires emergency management. We report a rare inborn error of metabolism presenting with severe acidemia secondary to ketoacidosis. Case presentation A 13-month-old boy developed severe respiratory distress during his first febrile episode. Laboratory tests revealed severe anion gap metabolic acidosis (pH 6.866, HCO 3 − 5.6 mmol/L, anion gap 23.4 mEq/L) with markedly elevated D-3-hydroxybutyrate (3HB 6,969 μmol/L). Acidosis improved following blood purification therapy, and he was discharged without sequelae. Metabolic testing suggested a ketone body utilization disorder. He was diagnosed with succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency as a compound heterozygote for a previously reported T435N variant and a novel L131_E132dup variant of OXCT1, with low SCOT activity in lymphocytes. Transient expression analysis of the L131_E132dup cDNA demonstrated no residual enzyme activity. Conclusions We compared data from patients with IKH requiring hospitalization and those with SCOT deficiency. Although 3HB levels did not differ significantly, patients with SCOT deficiency had significantly lower pH and HCO 3 − levels. In ketone body utilization disorders, once ketogenesis is upregulated, ketone bodies rapidly accumulate before renal compensation, leading to severe acidemia. In cases of disproportionate acidemia during ketoacidosis, ketone body utilization disorders should be considered.
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The association between hydration status and body composition in healthy children and adolescents

April 4, 2023

Priscilla Clayton, María Angélica Trak-Fellermeier, Alison Macchi, Rodolfo Galván, Zoran Bursac, Fatma Huffman-Ercanli, Juan Liuzzi, Cristina Palacios

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Objectives Children 10–20 years old in the US are currently obese, showing suboptimal hydration as 60% fail to meet the US Dietary Reference Intakes for water. Studies have shown a significant inverse association between hydration status and body composition in children, although most failed to use the Dual-X-Ray Absorptiometry Scan (DEXA), the gold standard for body composition. Limited studies used an objective marker to measure hydration, such as urine specific gravity (USG) from a 24-h urine collection. Therefore, this study aimed to examine the association between hydration status (measured from USG in a 24-h urine sample and assessed from three 24-h dietary recalls) and body fat % and lean mass (assessed from a DEXA scan) in children (10–13 years, n=34) and adolescents (18–20 years, n=34). Methods Body composition was measured using DEXA, total water intake (mL/d) was assessed from three 24-h dietary recalls and analyzed using the Nutrition Data System for Research (NDSR). Hydration status was objectively measured using USG via 24-h urine collection. Results Overall body fat % was 31.7 ± 7.31, total water intake was 1746 ± 762.0 mL/d, and USG score was 1.020 ± 0.011 uG. Linear regressions showed significance between total water intake and lean mass (B=12.2, p<0.05). Logistic regressions showed no significant association between body composition and USG and total water intake. Conclusions Findings showed total water intake was significantly associated with lean mass. Future research should be conducted to explore other objective markers of hydration and with a larger sample.
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Corrigendum to: Primary pigmented nodular adrenocortical disease (PPNAD): single centre experience

September 13, 2019

Saba Samad Memon, Kunal Thakkar, Virendra Patil, Swati Jadhav, Anurag R. Lila, Gwendolyn Fernandes, Tushar R. Bandgar, Nalini S. Shah

Article number: 20198888

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Journal Impact Factor	1	2024, Journal Citation Reports (Clarivate, 2025)
5-year Journal Impact Factor	1.4	2024, Journal Citation Reports (Clarivate, 2025)
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CiteScore	2.6	2024, Scopus (Elsevier B.V., 2025)
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Journal of Pediatric Endocrinology and Metabolism

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