A 26-day-old male infant presented with recurrent convulsions from 18 days of life. Laboratory investigations revealed severe hypomagnesemia (0.07 mmol/L) and hypocalcemia (1.65 mmol/L). Whole-exome sequencing was performed and identified compound heterozygous pathogenic variants in the TRPM6 gene, comprising c.5616G>A (p.Trp1872Ter) and a deletion of exons 20-23. The c.5616G>A variant was inherited from the father, and the exon 20-23 deletion was inherited from the mother; neither variant has been previously reported. Based on these findings, the diagnosis of primary hypomagnesemia with secondary hypocalcemia was confirmed. Oral magnesium sulfate supplementation was initiated, and no further convulsions occurred. At the 8-year follow-up, the patient exhibited persistent hypomagnesemia without other abnormalities. This case highlights that genetic testing helps confirm the diagnosis, and early magnesium supplementation effectively controls symptoms and prevents irreversible neurological impairment. 患儿男，日龄26 d，生后18 d起出现反复抽搐，实验室检查示严重低镁血症（0.07 mmol/L）及低钙血症（1.65 mmol/L）。全外显子组测序结果示患儿TRPM6基因存在c.5616G>A（p.Trp1872Ter）和外显子20~23缺失复合杂合致病性变异，其中前者来自父亲，后者来自母亲，且均未见文献报道。该患儿确诊为原发性肠性低镁血症，口服硫酸镁治疗后未再发抽搐。随访8年，仅表现为持续性低镁血症，余无异常。该病例提示，基因检测有助于明确诊断，早期补充镁剂可有效控制症状，并且可预防神经系统不可逆损伤。.

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive renal tubular disorder caused by mutations in the CLDN16 or CLDN19 genes. This case demonstrates the critical role of whole-exome sequencing (WES) in diagnosing FHHNC, particularly when novel mutations, such as the homozygous CLDN16 variant (c.351G > T, p.W117C) found in this patient, are identified, which expands the genetic understanding of this condition. A 17-year-old female presented with an 8-month history of persistent neck, shoulder, and upper limb pain that had worsened over the past month. Despite initial treatment for cervical degenerative disease at local hospitals, her symptoms showed minimal improvement. She also exhibited growth retardation, with a height of 145 cm (-2 SD), and experienced recurrent urinary tract infections, although she reported no visual disturbances or neurological symptoms. Laboratory tests revealed hypomagnesemia and elevated parathyroid hormone levels. Imaging studies confirmed bilateral nephrocalcinosis and a medullary sponge kidney. Genetic testing using WES identified a homozygous pathogenic mutation in CLDN16 (c.351G > T), which was further validated by Sanger sequencing in the patient and her heterozygous parents. During hospitalization, the patient received intravenous magnesium sulfate (2.5 g/day), oral calcium carbonate with vitamin D3 supplementation, and levofloxacin for urinary tract infection management. Upon discharge, she was maintained on oral magnesium oxide (500 mg twice daily) with regular monitoring of electrolyte levels and renal function. At the 2-year follow-up, the patient's serum magnesium levels improved but remained below the normal range. Hypercalciuria persisted, although her renal function was stable. Notably, there was no progression to end-stage renal disease, and her symptoms were better managed with ongoing treatment. This case underscores the importance of WES in the diagnosis of rare tubular disorders, especially when the clinical presentations are nonspecific. This finding highlights that CLDN16-related FHHNC can occur without ocular involvement, and this information may aid in differential diagnosis. Early and consistent magnesium supplementation appears to mitigate renal deterioration, emphasizing the need for prompt intervention. Additionally, this case reinforces the value of genetic counseling for families affected by autosomal recessive conditions.

Familiar hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare monogenic tubulopathy. Although some of its features are potentially harmful for skeletal homeostasis, this problem has not been systematically evaluated so far. To evaluate bone mineral density (BMD) in correlation with selected mineral parameters and bone turnover markers (BTMs) to determine the risk of bone mass loss in pediatric patients with FHHNC. The study comprised 28 FHHNC patients aged 4-18 years and 33 healthy, sex - and age matched controls. 6 FHHNC patients showed normal kidney function whereas the remaining 22 presented with CKD grade II- III (median eGFR 73 ml/min/1.73m2). In both groups, serum levels of calcium (sCa), phosphate (sP), magnesium (sMg), 25(OH)D3, 1.25 (OH)2D3, parathormone (PTH) and selected BTMs [BAP, OC, PINP, CTX-I, OPG, SCL, FGF23 and soluble Klotho protein (sKL)] as well as 24-hour urinary calcium excretion (24 h-uCa) were assessed. In addition, BMD of the lumbar spine by DXA method was evaluated. 3 (10.7%) of FHHNC patients showed low BMD (Z-score < -2). Although median Z-score was lower in FHHNC group in comparison to controls, the difference was not significant. FHHNC patients had significantly higher median PTH, 1.25(OH)2D3 and 24 h-uCa values as well as lower sMg. Of the BTMs, they had significantly higher FGF23 and CTX-I levels. CTX-I correlated positively with PTH, FGF23 and SCL but negatively with sMg. Moreover, FGF23 and PTH correlated negatively with sKL. Negative correlation between PTH and sMg was noticed. No significant correlations between measured BTMs and eGFR, sCa, sP, 25(OH)D3, 1.25 (OH)2D3 as well as 24 h uCa were found. None of BTMs significantly correlated with BMD. The results show that pediatric FHHNC patients, regardless of CKD may be at risk for increased bone resorption. Although its pathomechanism is complex, the trigger seems to be Mg depletion, aggravating secondary hyperparathyroidism and leading to the activation of osteolytic processes. However, their clinical significance is unknown, since only minority of patients show osteopenia. Therefore, follow-up of BMD and bone- related laboratory parameters including CTX-I seem to be essential in patients' monitoring, especially in adults with FHHNC.

原发性低镁血症伴继发性低钙血症（HSH）是一种罕见的常染色体隐性遗传病，是由于M型瞬时受体电位通道6（TRPM6）基因突变引起镁代谢障碍导致的。本文报道1例婴儿期起病的HSH患者的临床诊治经过及基因突变情况。患者表现为反复发作抽搐，伴颜面麻木、心悸、眼震等症状，化验检查显示持续严重低镁血症、低钙血症、低甲状旁腺激素血症；18岁时经基因检测发现存在TRPM6基因新发复杂杂合突变位点c.5083+1G>C和c.3209+2T>C。.

Patients with primary hyperparathyroidism (PHPT) are predisposed to hypomagnesemia as well as hypophosphatemia. In the current literature, scarce data was available on the clinical significance of hypomagnesemia in PHPT. The present study aimed to investigate the prevalence of hypomagnesemia and its association with complications of PHPT in a large nationwide cohort. A nationwide population-based retrospective study was conducted using anonymized data from the Turkish Ministry of Health National Electronic Database (E-nabız). The International Statistical Classification of Diseases and Related Health Problems (ICD)-10 codes were used to identify patient cohort with PHPT (E21) and 96,337 patients with PHPT were reviewed. Female patients (74,650 (77.488%)) comprised the vast majority of the cohort and the mean age was 58.3 ± 15.3 years. It was observed that 38,709 (40.181%) of the patients had osteoporosis and 11,153 (11.577%) had renal stones. The prevalence of hypomagnesemia was 23.783%. While the frequency of osteoporosis increased significantly in patients with hypomagnesemia (45.435% vs. 38.541%, p < 0.0001), there was no difference between the two groups in terms of the frequency of renal stones. In terms of its possible effects on the presence of hypomagnesemia, the presence of osteoporosis, hypercalcemia (≥ 11.2 mg/dL), lower eGFR levels (< 60 mL/min), higher PTH levels (≥ 150 pg/mL), and advanced age (≥ 50 years) were found to be significantly effective in multivariate logistic regression analyses. Hypomagnesemia is observed in approximately one-quarter of patients with PHPT. The presence of hypomagnesemia in a PHPT patient may indicate a more severe form of hyperparathyroidism and an increased risk of osteoporosis.