Journal of pediatric endocrinology & metabolism : JPEM最新文献

{"title":"Continuous glucose monitoring evidence of celiac disease in type 1 diabetes.","authors":"Jessica L Ruiz, Lisa A Asaro, Allison S Bernique, Elizabeth Healey, Jocelyn A Silvester, David Wypij, Michael S D Agus, Christina M Astley","doi":"10.1515/jpem-2025-0302","DOIUrl":"10.1515/jpem-2025-0302","url":null,"abstract":"<p><strong>Objectives: </strong>Quantitative glycemic metrics are needed to identify undiagnosed celiac disease in type 1 diabetes and reduce delays in celiac diagnosis. Celiac enteropathy drives malabsorption that increases the risk of prandial insulin-glucose mismatch and hypoglycemia. We assessed if children with type 1 diabetes and celiac disease have lower post-prandial glucose levels preceding celiac diagnosis vs. those without celiac disease, leveraging continuous glucose monitoring (CGM) data and a computational meal annotation algorithm.</p><p><strong>Methods: </strong>In this retrospective cohort study, children with type 1 diabetes <12 months duration using CGM, positive celiac serologies and biopsy confirmed celiac disease (n=16) were matched 1-to-4 to those with negative celiac serologies (n=60). Meals were computationally annotated in the 30-day window before serologies. Differences in post-prandial trough glucose and other prandial glycemic outcomes were assessed via mixed models.</p><p><strong>Results: </strong>Undiagnosed celiac disease was associated with a lower glucose rise from meal start to peak vs. no celiac disease (-8.9 %, 95 % CI, -14.9--2.5 %, p=0.009) and, during the first meal of the day, a lower fall from peak to trough (-9.3 %, 95 % CI, -16.5 %--1.5 %, p=0.02). There was no significant association between celiac disease and trough glucose, meal hypoglycemia or time hypoglycemic.</p><p><strong>Conclusions: </strong>Computational analysis revealed that blunted prandial glycemic trajectories, not hypoglycemia, are associated with undiagnosed celiac disease in children with type 1 diabetes using CGM. These findings challenge current guidelines, and future studies should validate and integrate these glycemic biomarkers into a CGM-based model for real-time prediction of celiac disease in type 1 diabetes.</p>","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145133190","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":"Wolcott-Rallison syndrome due to a novel homozygous missense variation (p.Gly602Val) in the exon 11 of <i>EIF2AK3</i> gene.","authors":"Bablu Kumar Gaur, Chirag Varshney, Aditi Rawat, Shruti Jain","doi":"10.1515/jpem-2025-0216","DOIUrl":"https://doi.org/10.1515/jpem-2025-0216","url":null,"abstract":"<p><strong>Objectives: </strong>To report an unusual case of Wolcott-Rallison syndrome (WRS) due to a novel homozygous missense mutation c.1805G>T (p.Gly602Val) in the Exon 11 of eukaryotic translation initiation factor 2 alpha kinase 3 (<i>EIF2AK3</i>) gene.</p><p><strong>Case presentation: </strong>A 2-month-old infant, born to a consanguineous marriage presented to PICU with the manifestation of severe diabetic ketoacidosis (severe hyperglycemia, pH 6.984 + ketones in urine). Genomic sequencing analyses detected a novel homozygous missense variation in the Exon 11 of the <i>EIF2AK3</i> gene that resulted in the amino acid substitution of valine for glycine at codon 602 (p.Gly602Val). A diagnosis of Wolcott-Rallison syndrome was confirmed. He was treated with fluid therapy and regular insulin infusion. The purpose of this case report is to highlight the novel mutation in the Exon 11 of the <i>EIF2AK3</i> gene and to raise awareness for screening of pathogenic genetic variants in the <i>EIF2AK3</i> gene in all patients with neonatal diabetes mellitus.</p><p><strong>Conclusions: </strong>In the evaluation of infants with diabetic ketoacidosis, genomic DNA sequencing analyses should be performed in all cases of neonatal diabetes mellitus for early diagnosis of Wolcott-Rallison syndrome.</p>","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145133202","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":"Novel MCT8 mutation: diagnostic value of T3/T4 ratio.","authors":"Azzeddine Laaraje, Abdelilah Radi, Soukaina Ait Hmadouch, Rachid Abilkassem","doi":"10.1515/jpem-2025-0446","DOIUrl":"https://doi.org/10.1515/jpem-2025-0446","url":null,"abstract":"<p><strong>Objectives: </strong>To highlight the diagnostic value of the T3/T4 ratio in <i>Allan-Herndon-Dudley syndrome</i> (AHDS) through a case report of a novel <i>SLC16A2</i> mutation.</p><p><strong>Case presentation: </strong>We report a 36-month-old boy with severe neurodevelopmental delay and axial hypotonia. Initial thyroid function tests at 10 months showed TSH at 4.77 μIU/mL and T3 at 8.9 pmol/L. Brain MRI was normal. At 28 months, genetic analysis identified a novel hemizygous c.1343_1344dup mutation in the <i>SLC16A2</i> gene. Follow-up thyroid profiling at 36 months revealed the characteristic AHDS pattern: elevated free T3 (10.20 pmol/L), low free T4 (7.80 pmol/L), and borderline high TSH (5.20 μIU/mL), with a T3/T4 ratio of 1.31 pmol/pmol.</p><p><strong>Conclusions: </strong>This case highlights the diagnostic value of the T3/T4 ratio (>0.75 pmol/pmol) as an essential biochemical marker of AHDS in any male infant presenting with unexplained developmental delay and hypotonia. A systematic diagnostic approach including early T3 measurement and T3/T4 ratio calculation should be applied in the initial evaluation of severe developmental delays, even in the presence of normal brain MRI findings, to avoid diagnostic delays in AHDS.</p>","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145116030","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":"Immunogenetic profiling of type 1 diabetes in Jordan: a case-control study on HLA-associated risk and protection.","authors":"Rasha Odeh, Abeer Alassaf, Hussam Alhawari, Hanan Jafar, Abdalla Awidi, Farah Bani Hani, Malik Sallam","doi":"10.1515/jpem-2025-0402","DOIUrl":"https://doi.org/10.1515/jpem-2025-0402","url":null,"abstract":"<p><strong>Objectives: </strong>To comprehensively investigate the association between HLA class II alleles and haplotypes with type 1 diabetes mellitus (T1DM) susceptibility in a Jordanian population.</p><p><strong>Methods: </strong>In this case-control study, 205 patients with clinically confirmed T1DM and 99 ethnically matched healthy controls were genotyped for <i>HLA-DRB1</i>, <i>DQA1</i>, and <i>DQB1</i> loci. Autoantibodies and thyroid function were evaluated. Haplotype frequencies were compared using the BIGDAWG R package, with odds ratios (ORs), 95 % confidence intervals (CIs), and false discovery rate (FDR) correction.</p><p><strong>Results: </strong><i>HLA-DRB1*03</i>:<i>01</i> (OR=4.94, p<0.001), <i>DRB1*04</i>:<i>02</i> (OR=3.87, p=0.003), and <i>DRB1*04</i>:<i>05</i> (case-only; p=0.002) were associated with T1DM. Strong associations were also observed for <i>DQA1*05</i>:<i>01</i> (OR=6.61, p<0.001) and <i>DQB1*02</i>:<i>01</i> (OR=5.70, p<0.001). Protective effects were identified for <i>DRB1*07</i>:<i>01</i>, <i>DRB1*15</i>:<i>02</i>, <i>DQA1*05</i>:<i>05</i>, and <i>DQB1*03</i>:<i>01</i> (all FDR<0.05). Among haplotypes, <i>DR3∼DQ2</i> conferred the greatest risk (OR=5.40, p<0.001), while <i>DRB1*11</i>:<i>04∼DQA1*05</i>:<i>05∼DQB1*03</i>:<i>01</i> was protective (OR=0.25, p=0.004). <i>DRB1*03</i>:<i>01</i> was associated with GAD65 autoantibodies and celiac serology. <i>DQA1*03</i>:<i>01</i> and <i>DQA1*05</i>:<i>01</i> were linked to thyroid autoantibodies. No significant differences in age or HbA1c at diagnosis were observed across HLA alleles.</p><p><strong>Conclusions: </strong>HLA class II variation was strongly associated with T1DM in Jordan, with <i>DR3∼DQ2</i> and <i>DR4</i> haplotypes driving susceptibility and <i>DRB1*07</i>, <i>DRB1*15</i>:<i>02</i>, and <i>DQB1*03</i>:<i>01</i> conferring protection, reflecting global patterns while highlighting region-specific features. These findings support incorporating HLA genotyping into T1DM risk assessment and suggest shared genetic links with other autoimmune diseases.</p>","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145088883","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":"Real-world effectiveness of sodium glucose transporter 2 inhibitors among youth with type 2 diabetes.","authors":"Michal Timkovski, Dhruva Patel, Elizabeth A Brown, Bliss Magella, Amy S Shah, Risa M Wolf","doi":"10.1515/jpem-2025-0243","DOIUrl":"https://doi.org/10.1515/jpem-2025-0243","url":null,"abstract":"<p><strong>Objectives: </strong>Clinical trials of sodium-glucose transporter 2 inhibitors (SGLT2i) in youth with type 2 diabetes (T2D) showed significant improvement in HbA1c% and fasting plasma glucose, yet there is limited real-world data on their use. This study sought to assess real-world use and effectiveness of SGLT2i medications in management of T2D in a diverse cohort of youth.</p><p><strong>Methods: </strong>This retrospective study analyzed youth newly prescribed a SGLT2i for management of T2D at two academic pediatric diabetes centers. Change in HbA1c, BMI, and insulin use from baseline to follow-up were evaluated for those taking SGLT2i added to their background diabetes treatment. Wilcoxon signed-rank test and McNemar's test were used to compare paired continuous and categorical variables, respectively.</p><p><strong>Results: </strong>A total of 81 patients with youth-onset T2D (mean age 17.3 years (SD 1.93), 63 % female, 51 % non-Hispanic Black, 13 % Hispanic, 33 % with private insurance) were prescribed SGLT2i. Among the 61 (75 %) reporting adherence or partial adherence at a median follow-up of 98 days, median HbA1c decreased from 8.4 to 7.1 % (p<0.001). There was a small but significant reduction in mean BMI Z-score from baseline to follow-up (2.66 to 2.57, p=0.0004). The proportion of patients prescribed basal insulin decreased from 44 to 34 % (p=0.03), and prandial insulin from 23 to 13 % (p=0.01).</p><p><strong>Conclusions: </strong>Real-world use of SGLT2i in youth with T2D is associated with decreased HbA1c levels and lower BMI Z-score and may also reduce use of insulin for youth with T2D.</p>","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145088855","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":"Impact of race and delayed adoption of diabetes technology on glycemia and partial remission in type 1 diabetes.","authors":"Adriana Chader-Gata Garcia, Komalpreet Kaur, Rashida Talib, Parissa Salemi, Joanna Fishbein, Benjamin Udoka Nwosu","doi":"10.1515/jpem-2025-0332","DOIUrl":"https://doi.org/10.1515/jpem-2025-0332","url":null,"abstract":"<p><strong>Objectives: </strong>Continuous glucose monitors (CGM) are the mainstay of glucose monitoring in type 1 diabetes (T1D). However, the impact of race/ethnicity and the timing of CGM adoption following T1D diagnosis is unclear. We examined the effect of race/ethnicity and CGM adoption on glycemia and partial remission (PR) in T1D.</p><p><strong>Methods: </strong>A 24-month longitudinal retrospective cohort study of youth with T1D who used Dexcom CGM G5/G6 between 2018 and 2022 was conducted. Subjects were classified as non-Hispanic White (NHW) or Other (Asian, Black/African American, Hispanic/Latino, or other). Glycemia was measured as %change in hemoglobin A1c (A1c) and time in range (TIR) from baseline to 24 months. PR was denoted as an insulin-dose-adjusted A1c (IDAA1c) value of ≤9. The statistical approach included the paired t-test, the Wilcoxon signed-rank test, and mixed effects models for repeated measures.</p><p><strong>Results: </strong>Early CGM adoption occurred in 90 % (61/68) of NHW subjects vs. 63 % (43/68) of the Other, p=0.0003. Early CGM adoption was associated with improved glycemia and PR as marked by a significantly greater %decrease in A1c, p=0.0008, and IDAA1c, p=0.0003, at 24 months following CGM adoption. Temporal trends in A1c and IDAA1c were significantly lower among NHW subjects, p<0.0001, and the probability of PR was significantly greater, p<0.0001. Early CGM adoption conferred a greater probability of PR than late CGM adoption, p<0.0001.</p><p><strong>Conclusions: </strong>Early adoption of diabetes technology should be accelerated in all children with T1D, particularly minority children, to reduce hyperglycemia, promote PR, and close the gap in diabetes care and complications in the United States.</p>","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145088871","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":"Spatiotemporal associations between incidence of type 1 diabetes and COVID-19 vaccination rates in children in Germany - a population-based ecological study.","authors":"Clemens Kamrath, Alexander J Eckert, Sarah Lignitz, Nikolas Hillenbrand, Axel Dost, Katharina Warncke, Daniela Klose, Karina Grohmann-Held, Reinhard W Holl, Joachim Rosenbauer","doi":"10.1515/jpem-2025-0189","DOIUrl":"https://doi.org/10.1515/jpem-2025-0189","url":null,"abstract":"<p><strong>Objectives: </strong>The incidence of type 1 diabetes (T1D) in children increased during the first two years of the COVID-19 pandemic and declined thereafter. It is not known whether the decline is associated with COVID-19 vaccination rates in children. This study investigates whether COVID-19 vaccination rates are associated with T1D incidence in children.</p><p><strong>Study design: </strong>Population-based ecological study of children with new-onset T1D in the years 2022 and 2023 from the German Prospective Diabetes Registry. COVID-19 vaccination rates (VR) for 2022 were obtained from the Digital Vaccination Rate Monitoring-Project of the Robert-Koch-Institute.</p><p><strong>Methods: </strong>Spatial Spearman correlation analysis between period-averaged COVID-19 VR and T1D standardized incidence ratios (SIR) per county were used for the year 2022. Bayesian conditional autoregressive (CAR) Poisson models, including a time lag of 0-12 months between COVID-19 VR and T1D SIR, were used to assess their association.</p><p><strong>Results: </strong>Data of 6,736 children and adolescents with new-onset T1D in the years 2022 and 2023 and of 4,208,377 vaccinated children aged 5-17 years across 336 German counties were analyzed. Neither the month-averaged spatial analysis (5-11 years: r=-0.029 [95%CI -0.136; 0.079]; 12-17 years: r=0.031 [95%CI -0.077; 0.138]) nor the spatiotemporal CAR models including time shifts of 0-12 months showed significant correlations between T1D SIR and COVID-19 VR.</p><p><strong>Conclusions: </strong>This study found no significant associations between childhood COVID-19 vaccination rates and the subsequent incidence of type 1 diabetes over the next 12 months. Further research is needed to investigate the relationship in younger children.</p>","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145088866","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":"Cardiometabolic outcomes in girls with premature adrenarche: a longitudinal analysis of typical vs. exaggerated presentations.","authors":"Gülcan Seymen, Murat İmal, Şükrü Hatun","doi":"10.1515/jpem-2025-0232","DOIUrl":"https://doi.org/10.1515/jpem-2025-0232","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate cardiometabolic risk factors in girls with premature adrenarche (PA), with a specific focus on outcomes based on adrenal androgen levels (typical vs. exaggerated adrenarche).</p><p><strong>Methods: </strong>Eighty-four girls with PA were followed from diagnosis to mid-puberty. Clinical, biochemical, and hormonal parameters were assessed at both time points. Participants were stratified based on dehydroepiandrosterone sulfate (DHEAS) levels: typical PA (40-130 μg/dL) and exaggerated adrenarche (>130 μg/dL). Age- and sex-matched controls (n=58) were included for pubertal comparisons.</p><p><strong>Results: </strong>At baseline, 25 % of PA girls were overweight/obese, and 22 % had elevated HOMA-IR. Exaggerated adrenarche was present in 19 % of subjects. By puberty, overweight/obesity prevalence rose to 33.3 %, with significant increases in fasting insulin, HOMA-IR, and declines in insulin sensitivity indices (QUICKI, FGIR). Comparisons with controls revealed significantly higher BMI, waist circumference, and insulin resistance among PA girls. However, there were no significant metabolic differences between exaggerated and typical PA groups, except for a higher waist circumference in the exaggerated group.</p><p><strong>Conclusions: </strong>Elevated mid-childhood DHEAS does not independently predict worsened metabolic outcomes by puberty. Baseline adiposity, not androgen level, is the principal determinant of insulin resistance and cardiometabolic risk in PA. Lifestyle interventions targeting weight management are crucial in mitigating future risk.</p>","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145088887","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":"Annual case counts and clinical characteristics of pediatric and adolescent patients with diabetes in Kenyatta National Hospital, Nairobi, Kenya. A 14 year retrospective study.","authors":"Phoebe Wamalwa, Lucy Mungai, Paul Laigong, Anjumanara Omar, Prisca Amolo","doi":"10.1515/jpem-2024-0626","DOIUrl":"https://doi.org/10.1515/jpem-2024-0626","url":null,"abstract":"<p><strong>Objectives: </strong>There is little data on prevalence, incidence rate and clinical characteristics on diabetes amongst the pediatric and adolescent group in sub-Saharan Africa. Therefore, this study aimed to document annual case counts, describe clinical characteristics, and assess loss to follow-up among pediatric and adolescent patients with diabetes at Kenyatta National Hospital.</p><p><strong>Methods: </strong>This was a hospital-based retrospective, descriptive study carried out at Kenyatta National Hospital, Pediatric Endocrinology Unit, between January 2008 and December 2021 amongst diabetic patients aged 25 years and below. Data was analyzed using Statistical Package for Social Science (SPSS) version 23.0.</p><p><strong>Results: </strong>Type 1 diabetes was the leading form of diabetes at 99.3 % (n=288). Most, 56.3 %, of cases of type 1 diabetes got diagnosed within the ages of 6-18 years, majority being 6-11 years. Most patients, 90.2 % presented in diabetic ketoacidosis (DKA) at initial diagnosis. There was a sustained increasing trend in type 1 diabetes with a notable dip in hospital visitations during covid time, the year 2020. Patients with type 1 diabetes took an average of 2.5 months and a median interval of 18 days from symptom onset to diagnosis. A third of the cases of type 1 diabetes, 31.25 %, were lost to follow up.</p><p><strong>Conclusions: </strong>The increasing cases of type 1 diabetes with delayed diagnosis require allocation of more resources and increased awareness creation. Measures need to be put in place to manage chronic conditions during pandemics. Hospital-based tracking system is required to prevent loss to follow up cases.</p>","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145082983","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":"Dual molecular genetic diagnosis with combined malonic and methylmalonic aciduria (CMAMMA): implications of coexisting genetic disorders on clinical presentation.","authors":"Melike Ersoy, Zehra Yavas Abali, Esra Deniz Papatya Cakir, Soner Erdin, Kanay Yararbas, Saygin Abali","doi":"10.1515/jpem-2025-0208","DOIUrl":"https://doi.org/10.1515/jpem-2025-0208","url":null,"abstract":"<p><strong>Objectives: </strong>Combined malonic and methylmalonic aciduria (CMAMMA) is an inherited metabolic disorder caused by <i>ACSF3</i> variants leading to malonyl-CoA synthetase (MCS) deficiency. Despite its well-defined genetic basis, the clinical spectrum of CMAMMA remains highly variable.</p><p><strong>Case presentation: </strong>This study reports six patients from three unrelated families, aged 12 days to 30 years, presenting with heterogeneous clinical manifestations. Exome sequencing (ES) identified a homozygous <i>ACSF3</i> variant, c.1470G>C [p.(Glu490Asp)], in five patients, and a <i>novel</i> variant, c.1145T>C [p.(Leu382Pro)], in one patient. Notably, in each family's index case, ES revealed additional pathogenic variants consistent with a dual molecular diagnosis: a homozygous <i>CHRNG</i> variant in one patient; compound heterozygous <i>BTD</i> variants in two siblings, confirming biotinidase deficiency; and a <i>novel CDK10</i> frameshift variant, c.520_521del [p.(Lys174Glyfs*34)], in another patient. Half of the patients with CMAMMA demonstrated mild to moderate developmental delay. Notably, the sibling with both CMAMMA and biotinidase deficiency exhibited developmental delay, whereas the sibling with isolated CMAMMA had normal development. Symptomatic individuals showed clinical improvement following dietary protein restriction and carnitine supplementation.</p><p><strong>Conclusions: </strong>These findings highlight that CMAMMA may cause developmental delay, emphasizing the importance of early diagnosis and treatment. Furthermore, in patients with atypical features, high-throughput sequencing technologies offer a comprehensive approach to identifying additional pathogenic variants in genes beyond <i>ACSF3.</i></p>","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083057","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}