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Background: Kidney stone disease (KSD) is characterized by an increasing prevalence worldwide, representing an important clinical issue and a financial burden for healthcare systems. A KSD-causing monogenic variant is traditionally expected in up to 30% of children and 1–5% of adults forming stones, confirmed by a strong connection between a positive family history and KSD. The insufficient use of genetic testing in these patients is associated with a lack of perceived benefit and a scarce awareness of inherited kidney diseases. Genetic testing has important practical implications, such as the possibility of earlier diagnoses, familial counseling, and tailored therapy, based on the evaluation of fine-mapped pathogenic variants. Our aim is to analyze the current evidence on genetic testing in KSD patients to whom genetic tests were applied without strict a priori selection criteria, to provide an overview of its diagnostic yield and factors potentially affecting it (such as the age of KSD onset, a familial history of KSD, consanguinity, and extrarenal features). Methods: A literature review was performed, selecting original articles published in the last 10 years concerning genetic investigations in patients affected by nephrolithiasis or nephrocalcinosis. Available data were subsequently extracted and analyzed. Results: In total, 13 studies on 1675 patients (77% pediatric populations) were included; 333 patients were determined to be affected by a monogenic disorder, with an overall yield of about 20%. The likelihood of a positive genetic finding was much higher in pediatric (26%) than adult populations (8%). Cystinuria was the most common diagnosis in both populations. After the removal of conditions that could be identified with a stone composition analysis or urinary chemistry investigation, the diagnostic yield dropped to 19% among pediatric patients and below 5% for adults. Conclusions: Genetic testing should be considered in KSD pediatric patients and in selected subgroups of adults with suggestive features when a diagnosis is not established after stone examination and blood as well as urine metabolic profiling. [ABSTRACT FROM AUTHOR]

Fanconi-Bickel syndrome (FBS) is a rare genetic disorder of carbohydrate metabolism due to pathogenic variants in SLC2A2, a gene encoding glucose transporter 2 (GLUT2), which leads to accumulation of glycogen in the kidney and liver. While consequential complex proximal tubular dysfunction is well acknowledged in the literature, long-term trajectories of kidney function in patients with FBS have not been well characterized, and kidney biopsy is performed infrequently. Here, we report on a patient with FBS followed from infancy through young adulthood who presented early on with hypercalciuria, phosphaturia, and hypophosphatemia, complicated by chronic kidney disease development during childhood. Kidney biopsy, in addition to a widespread glycogen accumulation in proximal tubular epithelial cells, demonstrated medullary nephrocalcinosis. Screening for nephrocalcinosis may be warranted in pediatric patients with FBS, along with close surveillance of their kidney function. [ABSTRACT FROM AUTHOR]

The primary hyperoxalurias (PH 1, 2, and 3) are rare autosomal recessive disorders of glyoxylate metabolism resulting in hepatic overproduction of oxalate. Clinical presentations that should prompt consideration of PH include kidney stones, nephrocalcinosis, and kidney failure of unknown etiology, especially with echogenic kidneys on ultrasound. PH1 is the most common and severe of the primary hyperoxalurias with a high incidence of kidney failure as early as infancy. Until the recent availability of a novel RNA interference (RNAi) agent, PH care was largely supportive of eventual need for kidney/liver transplantation in PH1 and PH2. Together with the Oxalosis and Hyperoxaluria Foundation, the authors developed a diagnostic algorithm for PH1 and in this report outline best clinical practices related to its early diagnosis, supportive treatment, and long-term management, including the use of the novel RNAi. PH1-focused approaches to dialysis and kidney/liver transplantation for PH patients with progression to chronic kidney disease/kidney failure and systemic oxalosis are suggested. Therapeutic advances for this devastating disease heighten the importance of early diagnosis and informed treatment. [ABSTRACT FROM AUTHOR]

Background: In patients with X-linked hypophosphatemia (XLH), conventional therapy with oral phosphate salts and active vitamin D has been associated with nephrocalcinosis. However, the nature of the relationships among XLH, its treatment, nephrocalcinosis, and kidney function remain poorly understood. Methods: Renal ultrasounds were performed and glomerular filtration rates were estimated (eGFR) at baseline in burosumab-naïve patients with XLH who participated in burosumab clinical trials (NCT02181764, NCT02526160, NCT02537431, NCT02163577, NCT02750618, NCT02915705) or enrolled in the XLH Disease Monitoring Program (XLH-DMP; NCT03651505). In this cross-sectional analysis, patient, disease, and treatment characteristics were described among patients with and without nephrocalcinosis. Results: The analysis included 196 children (mean [SD] age 7.6 [4.0] yr) and 318 adults (40.3 [13.1] yr). Mean (SD) height z-score was −1.9 (1.2) for children and −2.3 (1.7) for adults. Nearly all children (97%) and adults (94%) had previously received conventional therapy. Nephrocalcinosis was detected in 22% of children and 38% of adults. In children, reduced eGFR <90 mL/min/1.73 m2 was more prevalent in those with nephrocalcinosis (25%) than in those without (11%), a finding that was not observed in adults. Children with nephrocalcinosis had lower mean values of TmP/GFR (p<.05), serum 1,25(OH)2D (p<.05), and eGFR (p<.001) and higher mean serum calcium concentrations (p<.05) than did those without nephrocalcinosis. Adults with nephrocalcinosis had lower mean serum phosphorus (p<.01) and 1,25(OH)2D (p<.05) concentrations than those without. Exploratory logistic regression analyses revealed no significant associations between the presence of nephrocalcinosis and other described patient or disease characteristics. Conclusions: Nephrocalcinosis was observed in nearly one-quarter of children and more than one-third of adults with XLH. Further study is needed to better understand the predictors and long-term consequences of nephrocalcinosis, with surveillance for nephrocalcinosis remaining important in the management of XLH. Lay Summary: Conventionally, patients with X-linked hypophosphatemia (XLH) were treated with phosphate and vitamin D taken by mouth. However, this therapy might lead to a buildup of calcium in the kidney, called nephrocalcinosis. Here, we tried to better understand how XLH, conventional therapy, nephrocalcinosis, and kidney function are related. Nephrocalcinosis was detected with kidney ultrasounds. Kidney function, called the estimated glomerular filtration rate (eGFR), was determined using blood levels of creatinine. Patients had been part of burosumab clinical trials or part of the XLH Disease Monitoring Program. Data were collected from patients before they received burosumab. The study included 196 children and 318 adults. Almost all children and adults had received conventional therapy. 22% of children and 38% of adults had nephrocalcinosis. Some lab values were different among patients with vs without nephrocalcinosis. Children with nephrocalcinosis had significantly greater loss of phosphate by the kidneys, lower blood levels of the active form of vitamin D (1,25(OH)2D), lower eGFR, and higher blood levels of calcium than those without nephrocalcinosis. Adults with nephrocalcinosis had significantly lower blood levels of phosphorus and 1,25(OH)2D concentrations than those without. It remains important to monitor patients with XLH for nephrocalcinosis. Further study is needed to better understand nephrocalcinosis. [ABSTRACT FROM AUTHOR]

Aim. To determine the frequency and factors contributing to the formation of c-ma "hyperechoic pyramids" in children born with very low and extremely low body weight, as well as to assess kidney function in this contingent of children in a three-year catamnesis. Materials and methods. A comparative analysis of the ultrasound pattern of the urinary system was carried out in 756 premature babies, from birth to 3 years of age, two groups were identified: group I – 133 children who had hyperechoic pyramids in the neonatal period; group II – 643 children without hyperechoic pyramids in the neonatal period; group III – the comparison group – 3000 full-term neonates. Results. The symptom of "hyperechoic pyramids" was detected in 15% of premature babies (group I) by the end of 1 month of life (25±6 days), in full-term babies (group III) – in 23 at the age of the first 3–10 days of life. In 2% of premature infants up to 2 months of age, hyperechoic inclusions were diagnosed, giving an acoustic shadow, which were interpreted as kidney concretions. It was revealed that the need (100% vs 71%) and duration (9.7 days vs 2.8 days) for mechanical ventilation, drug load and frequency of artificial feeding (92% vs 19%) in the I group were higher than in the II group. By 12 months of age, signs of nephrocalcinosis with hypercalciuria in group I were detected in 74% of patients and by 36 months were preserved in 23%. In 2% children with renal nodules detected in the first months of life, these changes up to 36 months of life and by 3 years of age, the frequency in group I was 6.6%. Conclusion. In children born with very low and extremely low body weight, there is a high frequency of detection of "hyperechoic pyramids," which tends to decrease with the growth of the child. In some children, the changes are persistent with a risk of progression in the absence of proper observation and treatment. Among the aggravating external influences, a significant role belongs to long-term mechanical ventilation and oxygen dependence, high drug load by various groups of drugs, as well as artificial feeding in neonatal and infancy.

Background: Variants in SLC34A1 and SLC34A2 genes, which encode co-transporters NaPi2a and NaPi2c, respectively, can lead to hypophosphatemia due to renal phosphate loss. This condition results in hypercalcitriolemia and hypercalciuria, leading to formation of kidney stones and nephrocalcinosis. Phenotype is highly variable. Management includes hyperhydration, dietary modifications, and/or phosphate supplementation. Thiazides and azoles may be used, but randomized studies are needed to confirm their clinical efficacy. Methods: We conducted a retrospective study in the pediatric nephrology unit at Grenoble University Hospital from January 2010 to December 2023. The study aimed to describe clinical and biological symptoms of patients with confirmed SLC34A1 and SLC34A3 gene variants and their outcomes. Results: A total of 11 patients (9 females) from 6 different families had variants in the SLC34A1 (5 patients) and SLC34A3 (6 patients) genes. Median age at diagnosis was 72 [1–108] months. Average follow-up duration was 8.1 ± 4.5 years. Presenting symptom was nephrocalcinosis (4 cases), followed by renal colic (3 cases). At diagnosis, 90% of patients had hypercalciuria and 45% had hypercalcitriolemia. Management included hyperhydration and dietary advice. All patients showed favorable outcomes with normal growth and school attendance. One patient with an SLC34A3 variant showed regression of nephrocalcinosis. Kidney function remained normal. Conclusion: Clinical and biological manifestations of SLC34 gene variants are highly variable, even among siblings; therefore, management must be personalized. Hygienic and dietary measures (such as hyperhydration, a low sodium diet, and age-appropriate calcium intake) result in favorable outcomes in most cases. Use of azoles (e.g., fluconazole) appears to be a promising therapeutic option. [ABSTRACT FROM AUTHOR]

This review synthesises recent discoveries in the risk factors of nephrocalcinosis, with a particular focus on novel findings. Nephrocalcinosis, characterised by the deposition of calcium salts in the renal parenchyma, is linked to a variety of genetic, metabolic, dietetic, and environmental contributors. The study emphasises the critical role of advanced imaging techniques in diagnosis and the identification of new genetic mutations in genes such as CLCN5, CASR , and SLC34A3 as significant contributors to the condition. The paper highlights the importance of recognising these novel risk factors for better diagnosis, treatment, and prevention of nephrocalcinosis. It calls for further research to explore these new dimensions, particularly the genetic underpinnings and environmental exposures, to develop more effective management strategies and potentially prevent the onset of this complex renal condition.

Background: The heterogeneous features of enamel renal syndrome (ERS) make diagnosis and treatment challenging. The main symptoms are disturbed amelogenesis and nephrocalcinosis. Bi-allelic likely pathogenic (LP) or pathogenic (P) variants in FAM20A have been associated with the syndrome since 2012. Affected patients often receive extensive dental treatment because of deviant orofacial morphology. However, knowledge about long-term prognosis and treatment guidelines are still lacking. The complex nature of ERS might endanger both dental and general health. The purpose of this article is to highlight the risks of overlooking the symptoms of the syndrome, and to discuss management strategies, surveillance and prognosis. Case presentation: We report the management of a case with suspected ERS after initial dental treatment elsewhere with no adjustment for the syndrome. Dental treatment was revised and followed for 8 years. Complementary medical examinations were conducted, and ERS was genetically confirmed, revealing homozygosity for a LP c.755_757del, p.(Phe252del) variant in FAM20A. The nephrological investigation revealed medullary calcium deposits, normal renal function and hypophosphatemia. Urine analysis revealed hypocitraturia and hypocalciuria. Accordingly, the patient now medicates with potassium citrate to decrease the risk of progressive renal stone formation. Conclusion: We herein describe a patient with confirmed ERS with an 8-year follow-up. Diagnostic delay until adulthood led to complicated dental treatment. The results of nephrological investigations are presented. The importance of dental and medical multidisciplinary management in syndromic disorders affecting the formation of the enamel is also exemplified. The dental prognosis after rehabilitation is likely affected by anatomical variations and patient cooperation. The prognosis for renal function seems to be good. However, lifelong surveillance of renal function is recommended. Registration: The ethics committee in Uppsala, Sweden, determined that ethical approval was not necessary in this case (2019-04835). Informed consent was obtained from the participant in writing and is documented in the medical records.

Background: Nephrocalcinosis (NC) is characterized by an excessive accumulation of calcium deposits in the kidneys. In children, it is often incidentally discovered with an uncertain prognosis. Case-diagnosis/treatment: A 3-month-old girl suspected to have a milk protein allergy underwent an ultrasound that revealed increased echogenicity in the kidney pyramids suggestive of medullary NC. At the age of 18 months, imaging findings revealed not only hyperechogenicity in the medulla but also in the cortex. Over the course of a long follow-up, her kidneys maintained size within the upper limits but showed an increase by age 7. Genetic analysis identified PKHD1 variants, which required structural predictive tools to guide clinical diagnosis. Until the age of 7, her kidney function has remained intact; however, her prognosis is uncertain. Conclusions: NC in newborns is a rare condition, but its incidence is rising. Recurrent urinary infections or kidney stones may lead to kidney failure. A proactive approach in sporadic NC enables an early diagnosis to orientate clinical supervision and facilitates counseling to support family planning decisions. [ABSTRACT FROM AUTHOR]

Background. Dent’s disease (DD) is a rare X-linked recessive tubulopathy characterized by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis/nephrolithiasis and chronic kidney disease. With this manuscript, we reported three patients diagnosed as DD in our department in the last 10 years and thereby described the genetics, pathophysiology, clinical presentation, course and management of the disease. Cases. The first case was a male newborn who was consulted to our department after medullary nephrocalcinosis was detected. The second case was a 4-year-old boy who was treated with a diagnosis of urinary tract infection but was found to have proteinuria. Our last case was an 11-month-old male infant who was being followed up for recurrent urinary tract infection and who had millimetric crystalloids in the renal collecting system. Proteinuria and hypercalciuria were present in all cases. Variants were observed in the CLCN5 gene for the first two cases (c.1852G>A and c.1557+1G>T, respectively) and OCRL gene (c.952C>T) for the last case. All patients were recommended oral hydration and a low-salt diet, and hydrochlorothiazide and enalapril were started. No deterioration in kidney function was observed in any patient. Conclusion. DD is a disease that shows different phenotypes even among individuals with mutations in the same gene. Therefore, it should be considered in all patients with hypercalciuria, proteinuria, nephrolithiasis or nephrocalcinosis with/without proximal tubular dysfunction especially in the early childhood period. Classical treatments for hypercalciuria should be utilized, and a patient-based treatment plan should be drawn especially for proteinuria. [ABSTRACT FROM AUTHOR]

We report the case of a girl with a history of seizures associated with severe and persistent hypermagnesemia, hypocalcemia, hypercalciuria, metabolic acidosis, nephrocalcinosis, and progressive renal function deterioration leading to chronic renal failure stage 5 (ESCRD). A familial history of chronic renal disease, renal lithiasis, and paternal consanguinity prompted a genetic study identifying a pathogenic mutation in homozygosis c.446 G>A (p.R149Q) located in the exon 3 of the gen CLDN16 confirming the diagnosis of familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) with no severe ocular defects. The post-renal transplant is presented, showing good survival of the graft. [ABSTRACT FROM AUTHOR]

Background: Lumasiran is the first RNA interference (RNAi) therapy of primary hyperoxaluria type 1 (PH1). Here, we report on the rapid improvement and even disappearance of nephrocalcinosis after early lumasiran therapy. Case-diagnosis/treatment: In patient 1, PH1 was suspected due to incidental discovery of nephrocalcinosis stage 3 in a 4-month-old boy. Bilateral nephrocalcinosis stage 3 was diagnosed in patient 2 at 22 months concomitantly to acute pyelonephritis. Urinary oxalate (UOx) and glycolate (UGly) were increased in both patients allowing to start lumasiran therapy before genetic confirmation. Nephrocalcinosis started to improve and disappeared after 27 months and 1 year of treatment in patients 1 and 2, respectively. Conclusion: These cases illustrate the efficacy of early lumasiran therapy in infants to improve and even normalize nephrocalcinosis. As proposed in the 2023 European guidelines, the interest of starting treatment quickly without waiting for genetic confirmation may have an impact on long-term outcomes. [ABSTRACT FROM AUTHOR]

BackgroundX-linked hypophosphatemic rickets (XLH) is associated with uninhibited FGF23 activity, which leads to phosphaturia, hypophosphatemia and depressed active vitamin D (1,25OH2D) levels. Conventional treatment with phosphate supplements and vitamin D analogs may lead to hypercalciuria (HC), nephrocalcinosis (NC) and hyperparathyroidism. We investigated the effects of burosumab treatment, an anti-FGF23 monoclonal antibody recently approved for XLH, on these complications.MethodsThis retrospective study included children with XLH who were treated with burosumab for at least one year at one of three referral centers. Clinical and biochemical potential treatment outcomes were regularly followed, including multiple urine calcium measurements and NC severity score (0 = no NC, 3 = worse NC).ResultsTwenty-six (13 male) children aged 7.6 ± 3.9 years were followed for 27.5 ± 9.6 months. Mean serum phosphate levels rapidly increased from 2.67 ± 0.61 at baseline to 3.57 ± 0.53 mg/dL after 3 months (p 0.2 mg/mg) was detected in 2/26 (7.7%) patients before burosumab initiation, resolved in one and persisted, albeit improved, in the second. Two patients were newly diagnosed with HC, 15 and 3 months after therapy, which persisted in one of them despite dose reduction attempts. Seven patients had NC at baseline (mean score: 1.8 ± 0.34), but none showed deterioration or developed new NC.ConclusionIn children with XLH treated with burosumab, HC was an infrequent side effect and preexisting NC did not worsen.

BackgroundVitamin D is a vital lipophilic vitamin that plays a pivotal role in calcium regulation, bone metabolism, and overall health. It is of the utmost importance to maintain appropriate serum levels of vitamin D from the moment of birth. The recommended daily intake for infants under the age of 12 months is 400 IU. In Europe, vitamin D is available in two forms: as a medicinal product and as a food supplement. The food supplement market is experiencing rapid growth, yet it is characterised by a lack of harmonised regulations, which may give rise to potential risks associated with their widespread use. While food supplements are typically regarded as safe, there is a potential for adverse effects, particularly when dosages are not properly managed.Case report and managementThis report presents the case of a 22-month-old girl who developed nephrocalcinosis as a result of an overdose of vitamin D from a dietary supplement purchased online. The initial presentation was characterised by symptoms such as polydipsia, polyuria and decreased growth. It was subsequently revealed that the child had been receiving an excessively high dose of vitamin D, amounting to 25 times the recommended amount, over a period of seven months. Despite normal calcium levels and renal function at the time of presentation, ultrasound imaging revealed the presence of early-stage nephrocalcinosis. The treatment plan involved hospital admission, intravenous hydration, a thiazide diuretic, potassium citrate, and a low-calcium diet. The vitamin D supplement was ceased. Over the course of a year, the patient demonstrated recovery in growth and normalization of vitamin D levels, although nephrocalcinosis remained stable.ConclusionThis case study highlights the potential dangers of unsupervised vitamin D supplementation, emphasising the importance of healthcare professionals exercising vigilance in prescribing and advising on vitamin D use, particularly in children. Furthermore, it underscores the necessity of establishing a database to track long-term outcomes in paediatric vitamin D intoxication cases, given the rarity of such incidents. This would facilitate the development of appropriate treatment protocols and provide valuable information to parents.

Infantile hypercalcemia (IH) is a rare genetic disorder characterized by hypercalcemia, hypercalciuria, low parathyroid hormone, and nephrocalcinosis during the first months of life. Biallelic variants in the genes CYP24A1 and SCL34A1 cause IH1 and 2, respectively. We present the case of a newborn with an antenatal diagnosis of IH2 due to the identification of echogenic, yet normal-sized kidneys at 23 weeks gestation. Trio whole-exome sequencing initially identified only a heterozygous pathogenic variant in SLC34A1. Re-analysis of the exome data because of the clinical suspicion of IH2 revealed a 21-basepair deletion in trans that had initially been filtered out because of its high allele frequency. The diagnosis of IH2 enabled postnatal screening for hypercalcemia, present already at week 1, resulting in early treatment with phosphate supplementation and vitamin D avoidance. In the subsequent course, biochemical parameters were normalized, and the patient showed no obvious clinical complications of IH2, apart from the nephrocalcinosis. [ABSTRACT FROM AUTHOR]

Primary hyperoxaluria is a rare congenital autosomal recessive disorder disrupting the glyoxylate metabolism pathway in the liver. Type1 primary hyperoxaluria is caused by a deficiency in a specific liver enzyme namely, alanine glyoxylate-aminotransferase which catalyzes the conversion of glyoxylate to glycine. By the absence of this enzyme, glyoxylate is converted to oxalate and high oxalate level causes deposition of insoluble calcium oxalate crystals in different organs specifically kidneys. The disease usually manifested by recurrent nephrolithiasis and/or nephrocalcinosis leads to renal failure. This report describes an end-stage renal disease case of a 36-year-old Iranian woman without any history of nephrolithiasis who underwent kidney transplantation. She developed an early onset transplant kidney failure. The patient underwent kidney biopsy, which revealed oxalate nephropathy, accordingly the genetic study confirmed diagnosis of primary hyperoxaluria. This rare case shows how type 1 primary hyperoxaluria can develop after kidney transplantation without having any manifestation prior to transplantation [ABSTRACT FROM AUTHOR]

Background and Objective Apparent mineralocorticoid excess (AME) syndrome is an ultra-rare autosomal-recessive tubulopathy, caused by mutations in HSD11B2 , leading to excessive activation of the kidney mineralocorticoid receptor, and characterized by early-onset low-renin hypertension, hypokalemia, and risk of chronic kidney disease (CKD). To date, most reports included few patients, and none described patients from Israel. We aimed to describe AME patients from Israel and to review the relevant literature. Design Retrospective cohort study. Methods Clinical, laboratory, and molecular data from patients' records were collected. Results Five patients presented at early childhood with normal estimated glomerular filtration rate (eGFR), while 2 patients presented during late childhood with CKD. Molecular analysis revealed 2 novel homozygous mutations in HSD11B2. All patients presented with severe hypertension and hypokalemia. While all patients developed nephrocalcinosis, only 1 showed hypercalciuria. All individuals were managed with potassium supplements, mineralocorticoid receptor antagonists, and various antihypertensive medications. One patient survived cardiac arrest secondary to severe hyperkalemia. At last follow-up, those 5 patients who presented early exhibited normal eGFR and near-normal blood pressure, but 2 have hypertension complications. The 2 patients who presented with CKD progressed to end-stage kidney disease (ESKD) necessitating dialysis and kidney transplantation. Conclusions In this 11-year follow-up report of 2 Israeli families with AME, patients who presented early maintained long-term normal kidney function, while those who presented late progressed to ESKD. Nevertheless, despite early diagnosis and management, AME is commonly associated with serious complications of the disease or its treatment. [ABSTRACT FROM AUTHOR]

Background: Enamel renal syndrome is a rare genetic disorder transmitted through an autosomal recessive mode. It is featured by a hypoplastic amelogenesis imperfecta, delayed tooth eruption, gingival fibromatosis, and nephrocalcinosis. The aim of this study was to describe clinically, radiologically, and histologically the main features of enamel renal syndrome and to point out the role of dentists in early diagnosing this genetic disease. Materials and methods: Our case of enamel renal syndrome was initially described by clinical, radiographic, and genealogic data, then complemented by ultrasound examination of the kidneys and microscopic observation of gingivae. Results: The study showed the presence of amelogenesis imperfecta (AI), several teeth impaction, gingival hyperplasia, bilateral nephrocalcinosis, and multiple calcifications in pulp, gingiva, dental follicle, and kidneys. Conclusion: The patient was followed for a full mouth rehabilitation and also referred to a nephrology for global medical checkup. The dentist plays a key role in diagnosing genetic diseases and in referring patients for medical comprehensive care. [ABSTRACT FROM AUTHOR]

Nephrolithiasis (NL) is a common condition worldwide. The incidence of NL and nephrocalcinosis (NC) has been increasing, along with their associated morbidity and economic burden. The etiology of NL and NC is multifactorial and includes both environmental components and genetic components, with multiple studies showing high heritability. Causative gene variants have been detected in up to 32% of children with NL and NC. Children with NL and NC are genotypically heterogenous, but often phenotypically relatively homogenous, and there are subsequently little data on the predictors of genetic childhood NL and NC. Most genetic diseases associated with NL and NC are secondary to hypercalciuria, including those secondary to hypercalcemia, renal phosphate wasting, renal magnesium wasting, distal renal tubular acidosis (RTA), proximal tubulopathies, mixed or variable tubulopathies, Bartter syndrome, hyperaldosteronism and pseudohyperaldosteronism, and hyperparathyroidism and hypoparathyroidism. The remaining minority of genetic diseases associated with NL and NC are secondary to hyperoxaluria, cystinuria, hyperuricosuria, xanthinuria, other metabolic disorders, and multifactorial etiologies. Genome-wide association studies (GWAS) in adults have identified multiple polygenic traits associated with NL and NC, often involving genes that are involved in calcium, phosphorus, magnesium, and vitamin D homeostasis. Compared to adults, there is a relative paucity of studies in children with NL and NC. This review aims to focus on the genetic component of NL and NC in children. [ABSTRACT FROM AUTHOR]

The widespread introduction of molecular genetic research methods into health care practice has made it possible to diagnose rare microdeletion syndromes in patients with multiple congenital malformations. Aim of the study is to present the results of a literature search and demonstrate a clinical observation of Williams-Beuren syndrome in 10-month-old monochorionic twins with congenital malformations of the cardiovascular system in combination with kidney pathology and an additional spleen. Results. Williams-Beuren syndrome (WBS) is a rare congenital disorder characterized by specific craniofacial dysmorphisms (elphic face) and a hoarse voice in combination with cardiovascular damage, mental retardation, musculoskeletal disorders, and hypercalcemia. WBS occurs in the population with a frequency of 1:7,500-1000 infants. The presence of a specific phenotype is associated with a hemizygous microdeletion of the long arm of chromosome 7 at region 7q11.23. The size of the deletion varies from 1.5 to 1.8 Mb and results in the loss of several neighboring genes. The diagnosis is made syndromologically and confirmed by modern molecular cytogenetic methods. Pathologically significant WBS mutations include loss of the ELN gene and loss of neighboring genes such as LIMK1, RFC2, BAZ1B, GTF2I, STX1A, CLIP2, GTF2IRD, NCF. Haploinsufficiency of ELN gene is the main marker of WBS and causes insufficient synthesis of elastin protein, which leads to development of pathology of heart and blood vessels (elastin arteriopathy), disorders of connective apparatus of joints, abnormalities of vocal cords and skin. LIMK1 hemizygosity is associated with impaired visual-spatial constructive cognition. Deletion of the RFC2 gene can cause growth retardation and developmental delay. Reduced intelligence can be caused by a mutation of the GTF2I gene and hypercalcemia by a mutation of the BAZ1B gene. The phenotypic manifestations of WBS are also thought to be influenced by the reduced expression of flanking intact genes. The diagnosis, treatment, and adjustment of patients with WBS require an interdisciplinary team of specialists. The presented clinical case demonstrates multisystem pathology in 10-month-old monochorionic dizygotic twins in whom Williams-Beuren syndrome was clinically diagnosed and confirmed by FISH: ish del (7)(q11.23q11.23)(ELN-). Conclusion. To confirm the genetic component in congenital multisystem pathology, it is necessary to use modern molecular genetic diagnostic methods. Determination of genetic mutation, its size and origin is important for medical genetic counseling. Early confirmation of the WBS allows to make an individual prognosis of the child's life and development, as well as to determine in time the optimal methods of treatment and adaptation, and to advise the parents in planning the next birth of children in the family. [ABSTRACT FROM AUTHOR]

Background: Three types of primary hyperoxaluria (PH) are recognized. However, data on PH type 2 (PH2), caused by defects in the GRHPR gene, are limited. Methods: We reviewed the medical records of patients < 18 years of age with genetically-proven PH2 from seven centres across India to identify the age of onset, patterns of clinical presentation, short-term outcomes and genetic profile, and to determine if genotype–phenotype correlation exists. Results: We report 20 patients (all with nephrolithiasis or nephrocalcinosis) diagnosed to have PH2 at a median (IQR) age of 21.5 (7, 60) months. Consanguinity and family history of kidney stones were elicited in nine (45%) and eight (40%) patients, respectively. The median (IQR) serum creatinine at PH2 diagnosis was 0.45 (0.29, 0.56) mg/dL with the corresponding estimated glomerular filtration rate being 83 (60, 96) mL/1.73 m2/min. A mutational hotspot (c.494 G > A), rare in Caucasians, was identified in 12 (60%) patients. An intronic splice site variant (c.735-1G > A) was noted in five (25%) patients. Four (20%) patients required surgical intervention for stone removal. Major adverse kidney events (mortality or chronic kidney disease (CKD) stages 3–5) were noted in six (30%) patients at a median (IQR) follow-up of 12 (6, 27) months. Risk factors for CKD progression and genotype–phenotype correlation could not be established. Conclusions: PH2 should no longer be considered an innocuous disease, but rather a potentially aggressive disease with early age of presentation, and possible rapid progression to CKD stages 3–5 in childhood in some patients. A mutational hotspot (c.494 G > A variant) was identified in 60% of cases, but needs further exploration to decipher the genotype–phenotype correlation. [ABSTRACT FROM AUTHOR]

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A Japanese female in her 20 s with a history of self-induced vomiting was diagnosed with severe renal failure and referred to our department. She was extremely lean, with a body mass index of 9.6 kg/m2. Computed tomography showed increased brightness of the entire renal parenchyma; renal biopsy demonstrated prominent calcium deposition in the Bowman’s capsule and tubulointerstitial areas accompanied by collapsed glomeruli, severe interstitial fibrosis and tubular atrophy. Although the diagnosis was nephrocalcinosis, no underlying conditions were found. Despite the management of chronic kidney disease-mineral bone disorder and nutritional therapy, the patient developed uremia and initiated maintenance hemodialysis approximately two years after the first visit. Kidney disorders are commonly observed in patients with eating disorders and may occasionally lead to end-stage kidney disease. However, detailed investigations are few, especially regarding the histopathological conditions of these patients, and the precise mechanisms remain unclear. Nephrocalcinosis can cause end-stage kidney disease if extensive, as observed in the present case.

This retrospective study aimed to evaluate the metabolic and biochemical abnormalities in children with nephrocalcinosis to identify its important risk factors and better understand the disease pathophysiology. Data were collected from the medical records of 163 children diagnosed with nephrocalcinosis. Their clinical and laboratory characteristics at admission were recorded, and a 24-hour urinalysis was performed to measure parameters such as calcium, oxalate, citrate, uric acid, magnesium, and cystine. Family history of kidney stones and parental consanguinity were present in 58.8% and 58.2% of patients, respectively. The most common underlying conditions were hyperparathyroidism (24%), distal renal tubular acidosis (16.6%), and medullary sponge kidney (12.9%). The main abnormalities included hypocitraturia (65.2%), hypercalciuria (51.9%), hypomagnesuria (44.6%), hyperoxaluria (39.1%), hyperuricosuria (31.5%), vitamin D deficiency (30.06%), and metabolic acidosis (27%). Patients with kidney stones and failure to thrive had higher rates of hypercalciuria. Metabolic acidosis was more common in those with parental consanguinity and vitamin D deficiency. Renal failure at final follow-up was more evident in older patients, those with parental consanguinity, hypokalemia, acidosis, and hyperparathyroidism. End-stage renal disease was more frequent in patients with consanguineous parentage, hyperparathyroidism, hypokalemia, and acidosis. Parental consanguinity, family history of kidney stones, and urinary metabolic disorders are important risk factors for pediatric nephrocalcinosis. This highlights the need for genetic counseling, screening, and monitoring of biochemical abnormalities. Early diagnosis and timely treatment are crucial to maintain glomerular function and prevent kidney failure.

BackgroundX-linked hypophosphatemic rickets (XLH) is a rare genetic disease characterized by inappropriately elevated circulating fibroblast growth factor 23 (FGF-23) and subsequent urinary phosphate wasting. The primary clinical manifestations of XLH include short stature, lower extremity bowing, dental abscesses, and rickets. Historical treatment includes phosphate and vitamin D supplementation, but recently, targeted therapy with burosumab has gained widespread acceptance. Burosumab is an FGF-23 blocking antibody. Conventional therapy options have been associated with the development of nephrocalcinosis (NC), with reported rates varying between 33% and 80% in XLH patients. Previous studies have noted that the phosphate supplementation dose correlates with the presence of NC, although this finding is not consistent across studies. It remains unclear whether nephrocalcinosis occurs in patients now treated with burosumab. Our aim was to identify XLH-associated nephrocalcinosis risk factors in our cohort of children with XLH and provide an updated analysis in the era of burosumab.MethodsWe identified 13 children with XLH who received routine medical care for XLH at our institution between 2015 and 2023. All were initially treated with conventional therapy and were transitioned to burosumab either upon its US Food and Drug Administration (FDA) approval in 2018 or at 6 months of age if this occurred after 2018. All patients were routinely monitored and this included laboratory tests and renal ultrasonography. Phosphate and calcitriol dosages were regularly adjusted to minimize serum and urinary laboratory abnormalities. Burosumab was administered according to its FDA package insert directions. Medication doses and laboratory values were analyzed between the group with NC and the group without NC.ResultsThree patients were noted to have evidence of NC within the study timeline. Two children developed NC while receiving conventional therapy and one while prescribed burosumab. None of the variables, including a positive family history of XLH, average age at diagnosis of XLH, duration or dosage of treatment with conventional therapy, average age at the initiation of burosumab, and all measured laboratory values, were significantly different between the groups with and without NC. Female sex was the only identified significant risk factor for a diagnosis of XLH-associated NC.ConclusionXLH-associated NC remains a clinical concern even with modern treatment, although the traditional risk factors (dose of phosphate supplements and degree of urinary phosphate excretion) may not always correlate with the onset of nephrocalcinosis. XLH patients receiving burosumab, which has been hypothesized to eliminate the risk factors for NC, can still develop NC. It is important to continue screening patients treated with burosumab for nephrocalcinosis. In addition, more research is needed to better understand the risk factors that cause XLH-associated NC and determine whether children with XLH never exposed to conventional therapy will develop NC.

The widespread introduction of molecular genetic research methods into health care practice has made it possible to diagnose rare microdeletion syndromes in patients with multiple congenital malformations.. Aim of the study is to present the results of a literature search and demonstrate a clinical observation of Williams- Beuren syndrome in 10-month-old monochorionic twins with congenital malformations of the cardiovascular system in combination with kidney pathology and an additional spleen. Results. Williams- Beuren syndrome (WBS) is a rare congenital disorder characterized by specifi c craniofacial dysmorphisms (elphic face) and a hoarse voice in combination with cardiovascular damage, mental retardation, musculoskeletal disorders, and hypercalcemia. WBS occurs in the population with a frequency of 1:7,500-1000 infants. The presence of a specifi c phenotype is associated with a hemizygous microdeletion of the long arm of chromosome 7 at region 7q11.23. The size of the deletion varies from 1.5 to 1.8 Mb and results in the loss of several neighboring genes. The diagnosis is made syndromologically and confi rmed by modern molecular cytogenetic methods. Pathologically signifi cant WBS mutations include loss of the ELN gene and loss of neighboring genes such as LIMK1, RFC2, BAZ1B, GTF2I, STX1A, CLIP2, GTF2IRD, NCF. Haploinsuffi ciency of ELN gene is the main marker of WBS and causes insuffi cient synthesis of elastin protein, which leads to development of pathology of heart and blood vessels (elastin arteriopathy), disorders of connective apparatus of joints, abnormalities of vocal cords and skin. LIMK1 hemizygosity is associated with impaired visual- spatial constructive cognition. Deletion of the RFC2 gene can cause growth retardation and developmental delay. Reduced intelligence can be caused by a mutation of the GTF2I gene and hypercalcemia by a mutation of the BAZ1B gene. The phenotypic manifestations of WBS are also thought to be infl uenced by the reduced expression of fl anking intact genes. The diagnosis, treatment, and adjustment of patients with WBS require an interdisciplinary team of specialists. The presented clinical case demonstrates multisystem pathology in 10-month-old monochorionic dizygotic twins in whom Williams- Beuren syndrome was clinically diagnosed and confi rmed by FISH: ish del (7)(q11.23q11.23)(ELN-). Conclusion. To confi rm the genetic component in congenital multisystem pathology, it is necessary to use modern molecular genetic diagnostic methods. Determination of genetic mutation, its size and origin is important for medical genetic counseling. Early confi rmation of the WBS allows to make an individual prognosis of the child’s life and development, as well as to determine in time the optimal methods of treatment and adaptation, and to advise the parents in planning the next birth of children in the family.

Introduction: This study was designed to determine the mineral composition of calculi in nephrocalcinosis with nephrolithiasis, diagnose the underlying disease, and monitor the course of renal function in patients with nephrocalcinosis-nephrolithiasis. Methods: Renal calculi extruded in a series of 8 patients with nephrocalcinosis were analysed using Fourier transmission infrared spectrometry. In 4 patients, next-generation sequencing using a nephrocalcinosis-nephrolithiasis panel was performed to determine the nature of the underlying disease. In addition, longitudinal analysis of renal function was performed in all patients. Results: Seven patients revealed carbonate apatite as the sole constituent of renal calculi. One patient showed a mixed composition of dicalcium phosphate dihydrate/carbonate apatite at first analysis yet in subsequent episodes also had calculi composed of pure carbonate apatite. Further molecular analysis displayed distal renal tubular acidosis in 2 of 4 patients who consented to sequencing. No known genetic defect could be found in the other two cases. In line with prior reports, decline of renal function was dependent on underlying disease. Distal renal tubular acidosis revealed a progressive course of renal failure, whereas other causes showed stable renal function in long term analysis. Conclusion: Nephrocalcinosis with nephrolithiasis is a rare condition with heterogeneous aetiology. Yet mineral composition of renal calculi predominantly consisted of pure carbonate apatite. This uniform finding is similar to subcutaneous calcifications of various origins and might propose a general principle of tissue calcification. Progressive decline of renal function was found in distal renal tubular acidosis, whereas other conditions remained stable over time.

Abstract Background Hereditary hypophosphatemia rickets with hypercalciuria (HHRH) is a rare autosomal recessive disorder characterised by reduced renal phosphate reabsorption leading to hypophosphataemia, rickets and bone pain. Here, we present a case of HHRH in a Chinese boy. Case presentation We report a 11-year-old female proband, who was admitted to our hospital with bilateral genuvarum deformity and short stature. Computed Tomography (CT) showed kidney stones, blood tests showed hypophosphatemia, For a clear diagnosis, we employed high-throughput sequencing technology to screen for variants. Our gene sequencing approach encompassed whole exome sequencing, detection of exon and intron junction regions, and examination of a 20 bp region of adjacent introns. Flanking sequences are defined as ±50 bp upstream and downstream of the 5′ and 3′ ends of the coding region.The raw sequence data were compared to the known gene sequence data in publicly available sequence data bases using Burrows-Wheeler Aligner software (BWA, 0.7.12-r1039), and the pathogenic variant sites were annotated using Annovar. Subsequently, the suspected pathogenic variants were classified according to ACMG’s gene variation classification system. Simultaneously, unreported or clinically ambiguous pathogenic variants were predicted and annotated based on population databases. Any suspected pathogenic variants identified through this analysis were then validated using Sanger sequencing technology. At last, the proband and her affected sister carried pathogenic homozygous variant in the geneSLC34A3(exon 13, c.1402C > T; p.R468W). Their parents were both heterozygous carriers of the variant. Genetic testing revealed that the patient has anLRP5(exon 18, c.3917C > T; p.A1306V) variant of Uncertain significance, which is a rare homozygous variant. Conclusion This case report aims to raise awareness of the presenting characteristics of HHRH. The paper describes a unique case involving variants in both theSLC34A3andLRP5genes, which are inherited in an autosomal recessive manner. This combination of gene variants has not been previously reported in the literature. It is uncertain whether the presence of these two mutated genes in the same individual will result in more severe clinical symptoms. This report shows that an accurate diagnosis is critical, and with early diagnosis and correct treatment, patients will have a better prognosis.

Background: Furosemide is a drug widely used for several medical conditions and could be used without medical prescription. Furosemide-related nephrocalcinosis can occur regardless of age, although the risk is higher in premature infants. The defining characteristic of nephrocalcinosis is generalized calcium deposition in the kidney. The most useful imaging studies for evaluation are ultrasonography and computed tomography (more effective in detecting calcification). Case Presentation: A 32-year-old woman with a history of depressive syndrome was admitted for evaluation of fortuitously discovered nephrocalcinosis and hypokalemia. The studies performed revealed the presence of a metabolic alkalosis with discrete hyperreninism/hyperaldosteronism but normal ratio, normotension and urinary study showed elevated sodium, chloride, potassium and calcium fluctuating in different determinations. Surreptitious diuretic intake was suspected and urine analysis revealed doses equivalent to 80-120 mg. The patient was advised to discontinue all diuretic treatment; she was adequately supplemented with potassium and she was followed-up in outpatient clinics. During the follow-up, clinical and analytical improvement was noted, which led to the discontinuation of supplementation. Conclusion: Surreptitious diuretic intake is a clinical condition to rule out in patients with chronic hypokalemia, metabolic alkalosis with elevated urinary sodium and chloride. The relation between surreptitious diuretic intake and nephrocalcinosis has not been fully elucidated in adults.

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This article discusses a case study of a family in Iran who experienced a rare genetic disorder called familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC). The disorder is caused by a mutation in the CLDN16 gene and results in symptoms such as low levels of magnesium, high levels of calcium in the urine, and the formation of kidney stones. The study highlights the importance of genetic testing and counseling for affected individuals and their families, and provides valuable insights into the genetic basis of this condition. This is the first reported case of the CLDN16 gene mutation in Iran. [Extracted from the article]

Objective: The present study compared the clinical features of patients with primary Sjögren's syndrome (pSS) with and without nephrolithiasis and/or nephrocalcinosis to determine factors related to renal dysfunction. Methods: The clinical features of 68 patients with anti-Sjogren's syndrome antigen A (SSA)/Ro-antibody–positive pSS with and without nephrolithiasis and/or nephrocalcinosis who underwent abdominal computed tomography and/or ultrasonography were retrospectively analysed. Results: Of the 68 patients with anti-SSA-antibody–positive pSS, 23 (33%) had renal nephrolithiasis and/or nephrocalcinosis, whereas 45 (67%) did not. Fourteen (20%) patients had renal dysfunction at diagnostic imaging. Among five patients who underwent renal biopsy, four patients with renal nephrolithiasis and/or nephrocalcinosis were diagnosed with tubulointerstitial nephritis, and one without nephrolithiasis and/or nephrocalcinosis was diagnosed with minimal change nephrotic syndrome. Estimated glomerular filtration rate at diagnostic imaging was significantly lower in patients with than without nephrolithiasis and/or nephrocalcinosis group (P = 0.010). In addition to nephrolithiasis and/or nephrocalcinosis (odds ratio [OR], 3.467; P = 0.045), the gap between serum sodium and chloride concentrations (OR, 10.400; P = 0.012) and increased urinary β2-microglobulin (OR, 5.444; P = 0.033) were associated with renal dysfunction at the time of diagnostic imaging. Conclusion: Nephrolithiasis and/or nephrocalcinosis, normal anion gap metabolic acidosis, and tubulointerstitial damage are associated with renal dysfunction in patients with pSS. [ABSTRACT FROM AUTHOR]

Patients with mutations in Cldn16 suffer from familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC) which can lead to renal insufficiency. Mice lacking claudin-16 show hypomagnesemia and hypercalciuria, but no nephrocalcinosis. Calcium oxalate and calcium phosphate are the most common insoluble calcium salts that accumulate in the kidney in the case of nephrocalcinosis, however, the formation of these salts is less favored in acidic conditions. Therefore, urine acidification has been suggested to limit the formation of calcium deposits in the kidney. Assuming that urine acidification is causative for the absence of nephrocalcinosis in the claudin-16-deficient mouse model, we aimed to alkalinize the urine of these mice by the ablation of the subunit B1 of the vesicular ATPase in addition to claudin-16. In spite of an increased urinary pH in mice lacking claudin-16 and the B1 subunit, nephrocalcinosis did not develop. Thus, urinary acidification is not the only factor preventing nephrocalcinosis in claudin-16 deficient mice. [ABSTRACT FROM AUTHOR]

Introduction: This study was designed to determine the mineral composition of calculi in nephrocalcinosis with nephrolithiasis, diagnose the underlying disease, and monitor the course of renal function in patients with nephrocalcinosis-nephrolithiasis. Methods: Renal calculi extruded in a series of 8 patients with nephrocalcinosis were analysed using Fourier transmission infrared spectrometry. In 4 patients, next-generation sequencing using a nephrocalcinosis-nephrolithiasis panel was performed to determine the nature of the underlying disease. In addition, longitudinal analysis of renal function was performed in all patients. Results: Seven patients revealed carbonate apatite as the sole constituent of renal calculi. One patient showed a mixed composition of dicalcium phosphate dihydrate/carbonate apatite at first analysis yet in subsequent episodes also had calculi composed of pure carbonate apatite. Further molecular analysis displayed distal renal tubular acidosis in 2 of 4 patients who consented to sequencing. No known genetic defect could be found in the other two cases. In line with prior reports, decline of renal function was dependent on underlying disease. Distal renal tubular acidosis revealed a progressive course of renal failure, whereas other causes showed stable renal function in long term analysis. Conclusion: Nephrocalcinosis with nephrolithiasis is a rare condition with heterogeneous aetiology. Yet mineral composition of renal calculi predominantly consisted of pure carbonate apatite. This uniform finding is similar to subcutaneous calcifications of various origins and might propose a general principle of tissue calcification. Progressive decline of renal function was found in distal renal tubular acidosis, whereas other conditions remained stable over time. Plain Language Summary: Renal stones may occur in conditions that involve calcification of the kidney itself. In this case series, we chemically analysed these stones. In some cases, we also performed genetic tests. Interestingly, we found a similar composition in most stones, irrespective of the underlying disorder. This suggests a common mechanism of calcification. [ABSTRACT FROM AUTHOR]

Enamel renal gingival syndrome is a rare clinical condition characterized by the presence of amelogenesis imperfecta hypoplastic type, gingival fibromatosis and delayed tooth eruption, in addition to nephrocalcinosis with normal blood calcium levels. It is inherited as an autosomal recessive trait caused by mutations in the FAM20A gene located on chromosome 17q24.2. The purpose of this report is to describe a case of enamel renal gingival syndrome and discuss its distinct features and management. [ABSTRACT FROM AUTHOR]

Background: Furosemide is a drug widely used for several medical conditions and could be used without medical prescription. Furosemide-related nephrocalcinosis can occur regardless of age, although the risk is higher in premature infants. The defining characteristic of nephrocalcinosis is generalized calcium deposition in the kidney. The most useful imaging studies for evaluation are ultrasonography and computed tomography (more effective in detecting calcification). Case Presentation: A 32-year-old woman with a history of depressive syndrome was admitted for evaluation of fortuitously discovered nephrocalcinosis and hypokalemia. The studies performed revealed the presence of a metabolic alkalosis with discrete hyperreninism/hyperaldosteronism but normal ratio, normotension and urinary study showed elevated sodium, chloride, potassium and calcium fluctuating in different determinations. Surreptitious diuretic intake was suspected and urine analysis revealed doses equivalent to 80-120 mg. The patient was advised to discontinue all diuretic treatment; she was adequately supplemented with potassium and she was followed-up in outpatient clinics. During the follow-up, clinical and analytical improvement was noted, which led to the discontinuation of supplementation. Conclusion: Surreptitious diuretic intake is a clinical condition to rule out in patients with chronic hypokalemia, metabolic alkalosis with elevated urinary sodium and chloride. The relation between surreptitious diuretic intake and nephrocalcinosis has not been fully elucidated in adults. [ABSTRACT FROM AUTHOR]

Introduction: Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare genetic disorder. There are few descriptions of phenotype and genotype in pediatric patients, especially from Asia. Methods: We retrospectively reviewed the records of 11 patients who were diagnosed with FHHNC due to a common homozygous mutation in CLDN19, the gene encoding claudin 19, in the state of Sarawak, Malaysia. Results: Eleven patients from eight families, predominantly of Iban descent, were diagnosed with FHHNC at a median age of 7 years. These patients had an identical novel homozygous pathogenic variant in CLDN19, c427del. Seven patients (63.7%) had ocular abnormalities. All patients had nephrocalcinosis; hypomagnesemia and hypocalcemia were seen in 10 and 6 cases, respectively. One patient was asymptomatic at diagnosis. Progression to kidney failure was seen in two patients, at 7 and 15 years of age. Conclusions: The finding of a common novel mutation in non consanguineous families from the Iban population across different regions in the Sarawak state suggests a founder effect, underscoring the importance of genetic screening in children from this region presenting with unexplained ocular symptoms or electrolyte abnormalities associated with nephrocalcinosis, to facilitate early diagnosis and management of FHHNC. [ABSTRACT FROM AUTHOR]

Background: Nephrocalcinosis (NC) is a serious condition among neonates that needs proper management. The study aimed to detect the prevalence of nephrocalcinosis among preterm babies in Fallujah city, west of Iraq, and measure its association with a variety of risk factors. Methods: Thirty preterm cases were recruited from September to December of 2019. A pediatric radiologist performed an ultrasound on babies in the sample to detect nephrocalcinosis. Results: There were 30 neonate babies; 7 (23%) cases had nephrocalcinosis. The mean gestation weight was 1.6±0.4 Kg. About 6% of the neonates did not need an oxygen supply, 10% required steroids, 33% needed theophylline, 20% received vancomycin, 3% received diuretics, and 70% received gentamycin. There was a statistically non-significant association between gender and using oxygen, theophylline, steroids, vancomycin, and diuretics with the occurrence of nephrocalcinosis. Conclusion: Nephrocalcinosis among premature babies is a common disease and should be considered for screening. Treatment is mandatory to prevent its dangerous consequences. [ABSTRACT FROM AUTHOR]