Journal of pediatric endocrinology & metabolism : JPEM最新文献

{"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}

{"title":"Family experience with individuals of different ages and clinical presentations diagnosed with DI: do familial DI cases tolerate polyuria better?","authors":"Hakan Birinci, Emrullah Arslan, Tansu Değirmenci, Bumin N Dündar","doi":"10.1515/jpem-2025-0342","DOIUrl":"https://doi.org/10.1515/jpem-2025-0342","url":null,"abstract":"<p><strong>Objectives: </strong>Familial neurohypophyseal diabetes insipidus (DI) is a rare genetic disorder caused by vasopressin deficiency due to AVP gene mutations. This case report describes the genetic findings and clinical profiles of three generations within a family affected by hereditary central DI and managed with desmopressin.</p><p><strong>Case presentation: </strong>An 8-month-old male infant was admitted due to persistent polyuria and polydipsia that had been present since birth. History revealed a daily fluid intake of 7,200 mL and required 13 full diapers. The water deprivation test revealed a serum osmolality >300 mOsm/kg with a concurrently low urine osmolality (<300 mOsm/kg), confirming the diagnosis of DI. Desmopressin therapy was initiated for the patient. Using next-generation sequencing, a heterozygous variant c.329G>A (p.Cys110Tyr) was detected in the AVP gene. Following our patient's diagnosis, we evaluated first cousin once removed (on the maternal side) for similar symptoms. Upon identification of the heterozygous AVP variant via next-generation sequencing, desmopressin treatment was started. The same variant was detected in our patient's grandfather, mother, aunt, great-uncle, and first cousin once removed. Polyuria and polydipsia were present in all patients included in our case series. The grandfather and great-uncle, who were initially diagnosed, experienced delayed diagnosis and later developed renal complications. In contrast, the following generations of the family were diagnosed early.</p><p><strong>Conclusions: </strong>In familial cases, parents are often familiar with the clinical features of DI, allowing them to ensure adequate hydration, manage polyuria, and minimize the risk of dehydration. However, early diagnosis reduces the risk of long-term complications and enables effective family screening, allowing identification of previously unrecognized mild cases.</p>","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145077192","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":"A disease that is difficult to predict: regional distribution and phenotypic, histopathological and genetic findings in McArdle disease.","authors":"Bahattin Erdoğan, Gonca Kılıç Yıldırım, Ezgi Susam, Aziz Serhat Baykara","doi":"10.1515/jpem-2024-0622","DOIUrl":"https://doi.org/10.1515/jpem-2024-0622","url":null,"abstract":"<p><strong>Objectives: </strong>McArdle disease (also known as glycogen storage disease type V) is a rare metabolic myopathy that is caused by myophosphorylase deficiency, leading to impaired glycogenolysis in skeletal muscles. This study explored the clinical, histopathological, and genetic landscape of McArdle disease in a regional cohort from Turkey, emphasizing diagnostic and management challenges.</p><p><strong>Methods and results: </strong>A retrospective analysis was conducted on 350 muscle biopsies performed between 2013 and 2024 in a tertiary care center. Seven patients (2.1 %) were diagnosed with McArdle disease. The clinical features included exercise intolerance (100 %), muscle pain (75 %), and the second wind phenomenon (62.5 %). Two patients presented with acute renal failure due to rhabdomyolysis with myoglobinuria, leading to metabolic acidosis. Histopathological findings revealed glycogen accumulation in subsarcolemmal vacuoles and absent myophosphorylase activity in all cases. Genetic analysis identified five distinct <i>PYGM</i> pathogenic variants, including c.808C>T (p.Arg270Ter) and c.2262del (p.Lys754fs). These findings highlight the phenotypic and genetic heterogeneity of McArdle disease.</p><p><strong>Conclusions: </strong>McArdle disease remains underdiagnosed due to its variable clinical presentation and limited access to advanced diagnostic tools. This study underscores the importance of a multidisciplinary approach that integrates clinical assessment, muscle biopsy, and molecular analysis. Increased awareness and training among healthcare providers are critical for early recognition and intervention. Future research should focus on expanding genetic databases and exploring targeted therapies to improve outcomes in this challenging condition.</p>","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145077193","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":"Investigation of the association between nitric oxide synthase gene variants and NAFLD in adolescents with obesity.","authors":"Sevde Hasanoğlu Sayın, İbrahim Kandemir, Yasemin Oyacı, Shahri Khudiyeva, Memduh Şahin, Aylin Yetim Şahin, Sacide Pehlivan","doi":"10.1515/jpem-2025-0229","DOIUrl":"https://doi.org/10.1515/jpem-2025-0229","url":null,"abstract":"<p><strong>Objectives: </strong>The present study aimed to investigate whether nitric oxide synthase (<i>NOS</i>) enzyme gene variants (<i>iNOS</i> rs1060826, <i>eNOS</i> rs1799983, <i>eNOS</i> 27-bp VNTR) play a role in the etiopathogenesis of nonalcoholic fatty liver (NAFLD) in adolescents.</p><p><strong>Methods: </strong>This cross-sectional study was conducted with obese adolescents [body mass index (BMI) standard deviation score (SDS) ≥2] aged 10-19 years (104 individuals) and age- and sex-matched healthy individuals (64 individuals) whose presence of NAFLD was determined by ultrasound. The <i>iNOS</i> rs1060826 and <i>eNOS</i> rs1799983 variants were performed by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method, and the <i>eNOS</i> 27-bp VNTR variant was analyzed using the PCR method. The genotypes detected were compared between the patient group and the healthy controls and with the clinical parameters of the patients.</p><p><strong>Results: </strong><i>iNOS</i> rs1060826 and <i>eNOS</i> rs1799983 were independent of obesity, whereas <i>eNOS</i> 27-bp VNTR was independent of NAFLD. However, in the obese group, especially in those with NAFLD (+), the <i>iNOS</i> rs1060826 GG genotype was found to be associated with lower diastolic blood pressure (DBP) (p=0.011). Compared with the clinical parameters, insulin resistance (HOMA-IR) was higher in those carrying the <i>eNOS</i> rs1799983 gene variant-TT genotype in the NAFLD (+) group (p=0.051).</p><p><strong>Conclusions: </strong>While the three functional gene variants of the NOS enzyme did not show a significant difference in terms of genotype between patients and healthy controls, it was determined that both the <i>iNOS</i> rs1060826 gene variant-GG allele was associated with low DBP and HOMA-IR may be higher in those carrying the <i>eNOS</i> rs1799983 gene variant TT genotype in NAFLD (+) patients. The <i>iNOS</i> rs1060826 polymorphism is a potentially important genetic variant that may influence DBP regulation through its effects on nitric oxide production.</p>","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145077178","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":"Compound heterozygous <i>ROBO1</i> gene variants in a neonate with congenital hypopituitarism, dysmorphic features and midline abnormalities: a case report and review of the literature.","authors":"Panagiota Markopoulou, Amalia Sertedaki, Eirini Nikaina, Maria Binou, Ioanna Farakla, Tania Siahanidou, Christina Kanaka-Gantenbein","doi":"10.1515/jpem-2025-0086","DOIUrl":"https://doi.org/10.1515/jpem-2025-0086","url":null,"abstract":"<p><strong>Objectives: </strong>The majority of congenital hypopituitarism (CH) cases remain genetically unexplained. The transmembrane receptor Roundabout-1 (<i>ROBO1</i>), activated through interaction with SLIT-family proteins, plays crucial role in axonal guidance, branching, targeting, and midline axonal crossing. <i>ROBO1</i> variants have been associated with pituitary stalk interruption syndrome and highly variable pituitary-phenotypes, ranging from isolated growth hormone deficiency (IGHD) to combined pituitary hormone deficiency (CPHD). This study aimed to investigate the genetic basis of CH in a newborn and to review current evidence linking <i>ROBO1</i> variants with CH.</p><p><strong>Case presentation: </strong>We report the presence of two <i>ROBO1</i> variants in compound heterozygosity, the NM_002941:c.2914G>A, p.(Ala972Thr) and the novel NM_002941:c.3757G>A, p.(Val1253Met), as well as the identification of the novel <i>NOTCH3</i> variant NM_000435:c.1505C>T, p.(Ser502Phe) and the novel <i>GPR161</i> variant NM_001375883.1:c.1117C>T, p.(His373Tyr), in a newborn with CPHD, dysmorphic features and midline abnormalities.</p><p><strong>Conclusions: </strong>This case, together with accumulating evidence, supports <i>ROBO1</i> as a potential causative gene for CH. <i>ROBO1</i> should be considered during genetic evaluation of patients with CH and midline abnormalities. The co-occurrence of <i>NOTCH3</i> and <i>GPR161</i> variants raises the possibility of an oligogenic or multigenic etiology. The cross-talk between ROBO/SLIT and NOTCH signaling pathways may contribute to the complex phenotype observed and warrants further functional investigation.</p>","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144986437","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":"Atypical pediatric presentation of hyperparathyroidism: CDC73 gene mutation and parathyroid carcinoma.","authors":"Emel Hatun Aytaç Kaplan, Mehmet Çakmak, M Banu Yilmaz Özgüven, Şeyma Tuna Şentürk, Hasan Önal, Serdar Bozlak, Zümrüt Kocabey Sütçü","doi":"10.1515/jpem-2025-0367","DOIUrl":"https://doi.org/10.1515/jpem-2025-0367","url":null,"abstract":"<p><strong>Objectives: </strong>Parathyroid carcinoma is the rarest etiological cause of primary hyperparathyroidism and is exceedingly rare in the pediatric population. Clinical manifestations include severe hypercalcemia, pathological fractures, and bone pain. Diagnosis is typically established through surgical intervention and histopathological examination; however, genetic analyses can also support the diagnosis.</p><p><strong>Case presentation: </strong>A 10-year-10-month-old female presented with fatigue, leg pain, and a pathological fracture in her left forearm. Laboratory tests revealed hypercalcemia, hypophosphatemic hypercalcemia, and hyperparathyroidism. Imaging studies identified a 17 mm hypervascular hypoechoic lesion in the left paratracheal area. Surgical intervention included left inferior and superior parathyroidectomy and left thyroidectomy. Histopathology showed atypical parathyroid neoplasia and thyroid hyperplasia. Genetic testing revealed a pathogenic CDC73 mutation (p.E48*, c.142G>T). The patient is under regular follow-up for hyperparathyroidism-jaw tumor syndrome (HPT-JT) and parathyroid carcinoma.</p><p><strong>Conclusions: </strong>This case highlights the importance of early genetic testing in pediatric primary hyperparathyroidism (PHP), particularly for detecting CDC73 gene mutations associated with hyperparathyroidism-jaw tumor syndrome (HPT-JT). Early diagnosis allows for timely intervention, surgical planning, and long-term surveillance to manage potential complications such as parathyroid carcinoma and ossifying fibromas.</p>","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144986352","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":"Pseudohypertriglyceridemia as a clue: clinical and genetic spectrum of glycerol kinase deficiency in three pediatric cases.","authors":"Cemre Kara, Pınar Kılıçdağı Çanakcı, Engin Köse, Şule Haskoloğlu, Fatma Tuba Eminoğlu","doi":"10.1515/jpem-2025-0275","DOIUrl":"https://doi.org/10.1515/jpem-2025-0275","url":null,"abstract":"<p><strong>Objectives: </strong>Glycerol kinase deficiency (GKD) is a rare X-linked metabolic disorder caused by pathogenic variants in the GK gene. It can be present in either isolated or complex forms and often mimics primary hyperlipidemia, leading to diagnostic challenges and unnecessary treatment. This study aims to highlight the phenotypic variability and diagnostic features of GKD through a case series.</p><p><strong>Case presentation: </strong>We describe three pediatric patients diagnosed with GKD. Two siblings with isolated GKD presented with persistent, asymptomatic hypertriglyceridemia, confirmed by glyceroluria and genetic testing revealing a hemizygous c.213_214delAT (p.Cys72Ter) mutation. The third patient, diagnosed with complex GKD, presented in infancy with multisystem involvement, including immunodeficiency, hypotonia, splenic abscesses, and elevated and creatine kinase levels. Genetic analysis revealed a 6.9 Mb contiguous deletion spanning Xp21.2-Xp11.4. In all cases, elevated triglyceride levels were unresponsive to therapy, and serum samples lacked lipemic appearance. Lipid-lowering treatments were discontinued following diagnosis, with no adverse outcomes.</p><p><strong>Conclusions: </strong>This case series underscores the clinical and genetic heterogeneity of GKD. Urinary glycerol analysis and the absence of serum lipemia are key diagnostic clues. Early recognition is essential to prevent misdiagnosis and guide appropriate management, particularly in treatment-resistant hypertriglyceridemia.</p>","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755573","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":"Phenotypic variation among four members in a family with DAX1 deficiency.","authors":"Yuko Seki, Haruna Kakimoto, Izumi Tamada, Shozo Oku, Satoshi Morita, Minako Tokunaga, Michiyo Mizota, Naoko Amano, Noboru Uchida, Tomonobu Hasegawa, Yasuhiro Okamoto","doi":"10.1515/jpem-2025-0063","DOIUrl":"https://doi.org/10.1515/jpem-2025-0063","url":null,"abstract":"<p><strong>Objectives: </strong>To describe four members of a family with DAX1 deficiency caused by a novel <i>NR0B1</i>variant.</p><p><strong>Case presentation: </strong>All family members carried a novel hemizygous <i>NR0B1</i> variant, p.Gln318Alafs*71. The elder brother, aged 13 years, developed an adrenal crisis at the age of 3 years. The third brother, aged 4 years, showed a relatively low cortisol response to the short Synacthen test, but exhibited no clinical signs of adrenal insufficiency. The youngest brother developed an adrenal crisis at the age of 16 days. Additionally, their 14-year-old cousin was diagnosed with DAX1 deficiency based on skin pigmentation and family history.</p><p><strong>Conclusions: </strong>Despite carrying the same <i>NR0B1</i> variant, the initial symptoms and age of adrenal insufficiency onset varied among the four members of this family. Male members with a family history of DAX1 deficiency should be confirmed genetically as possible.</p>","PeriodicalId":520684,"journal":{"name":"Journal of pediatric endocrinology & metabolism : JPEM","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144736641","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":"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}