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Background: Proximal renal tubular dysfunction occurs during diabetic ketoacidosis (DKA) in type 1 diabetes. However, only a few studies have reported on the multiple proximal renal tubular functions simultaneously. Moreover, to the best of our knowledge, distal renal tubular function has not yet been investigated. Methods: Patients with newly diagnosed type 1 diabetes mellitus were classified into those with DKA and those without DKA, and their proximal and distal renal tubular functions were investigated. The diagnostic criteria for DKA were blood glucose > 200 mg/dL, blood pH < 7.3 or HCO3– < 15 mEq/L, and urine ketone body positivity. Results: Six patients with DKA and five patients without DKA were included. In patients with DKA, urinary β2-microglobulin levels were significantly higher, while blood pH, HCO3–, and tubular reabsorption of phosphorus were significantly lower than in those without DKA. There were no significant differences in blood glucose, HbA1c, serum phosphorus, urinary N-acetyl-beta-glucosaminidase, and urinary amino acid excretion between patients with and without DKA. Elevated NH3 levels and impaired urinary acidification were not observed in patients with and without DKA. Conclusions: In patients with newly diagnosed type 1 diabetes mellitus complicated with DKA, multiple proximal renal tubular dysfunctions occur simultaneously, suggesting transient Fanconi syndrome. Distal renal tubular acidosis was unlikely. The diagnostic criteria for DKA are appropriate also in the view of proximal renal tubular dysfunction and are considered suggestive of pathophysiological factors that may cause proximal renal tubular dysfunction. [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]

Background: Ifosfamide-induced Fanconi syndrome is a relatively infrequent complication that generally occurs in young patients with a high cumulative dose of ifosfamide; and is commonly characterized by glycosuria, proteinuria, electrolyte abnormalities, and a normal anion gap metabolic acidosis. Case Presentation: In this study, we present the case of a 16-year-old male patient with of osteosarcoma of the right femur with pulmonary metastasis, who received ifosfamide as part of chemotherapy 1 year and 2 months ago and required hospitalization for cellulitis. During inpatient management, he presented with hypokalemia, hypophosphatemia, polyuria, glycosuria, and proteinuria, by which he was diagnosed with Fanconi syndrome and nephrogenic diabetes insipidus, induced by ifosfamide. Management was focused on the control of the internal environment and use of potassium supplements and potassium-sparing diuretics. Conclusion: Patients receiving ifosfamide should be periodically monitored for kidney function and internal environment to detect any potential complications. It is thus important to carefully observe the cumulative dose of ifosfamide to prevent its associated nephrotoxicity, since its appearance can impoverish the prognosis in patients with neoplasms. Therefore, physicians should always be aware about the possibility of nephrotoxicity development. [ABSTRACT FROM AUTHOR]

Abstract Background Proximal renal tubular dysfunction occurs during diabetic ketoacidosis (DKA) in type 1 diabetes. However, only a few studies have reported on the multiple proximal renal tubular functions simultaneously. Moreover, to the best of our knowledge, distal renal tubular function has not yet been investigated. Methods Patients with newly diagnosed type 1 diabetes mellitus were classified into those with DKA and those without DKA, and their proximal and distal renal tubular functions were investigated. The diagnostic criteria for DKA were blood glucose > 200 mg/dL, blood pH

Abstract Autosomal dominant Fanconi syndrome due to a GATM variant (GATM‐FS), causes accumulation of misfolded arginine‐glycine amidinotransferase (AGAT) in proximal renal tubules leading to cellular injury. GATM‐FS presents during childhood and progresses to end‐stage kidney disease (ESKD) in adults. We study creatine metabolism in two individuals of unrelated families with a known GATM variant and the effect of creatine supplementation in kidney organoids. Plasma and urine metabolites were measured by mass spectrometry. Brain creatine was assessed by magnetic resonance spectroscopy (MRS). Guanidinoacetate (GAA) synthesis by the AGAT mutant was measured in patient‐derived immortalized lymphocytes using stable isotopes of arginine and glycine. The effect of creatine on GATM expression was assessed in human kidney cells and organoids. Several family members from two unrelated families were diagnosed with Fanconi syndrome and had the c.1022C>T (p. P341L) variant in GATM. Two affected individuals in both families had moderately reduced plasma GAA levels. In comparison to wild‐type cells, GAA synthesis by patient‐derived GATMP341L+/− lymphoblastoid cell lines (LCL) was reduced, but not absent as in GATM cells from a patient with creatine deficiency syndrome. In vitro studies on human kidney organoids revealed reduced AGAT expression after treatment with creatine. Finally, we showed in one patient that creatine supplementation (5 g daily) substantially increased plasma creatine levels. We report low plasma and urine GAA in patients with autosomal dominant GATM‐FS and show that creatine downregulates AGAT in human kidney cells.

Background: Ifosfamide-induced Fanconi syndrome is a relatively infrequent complication that generally occurs in young patients with a high cumulative dose of ifosfamide; and is commonly characterized by glycosuria, proteinuria, electrolyte abnormalities, and a normal anion gap metabolic acidosis. Case Presentation: In this study, we present the case of a 16-year-old male patient with of osteosarcoma of the right femur with pulmonary metastasis, who received ifosfamide as part of chemotherapy 1 year and 2 months ago and required hospitalization for cellulitis. During inpatient management, he presented with hypokalemia, hypophosphatemia, polyuria, glycosuria, and proteinuria, by which he was diagnosed with Fanconi syndrome and nephrogenic diabetes insipidus, induced by ifosfamide. Management was focused on the control of the internal environment and use of potassium supplements and potassium-sparing diuretics. Conclusion: Patients receiving ifosfamide should be periodically monitored for kidney function and internal environment to detect any potential complications. It is thus important to carefully observe the cumulative dose of ifosfamide to prevent its associated nephrotoxicity, since its appearance can impoverish the prognosis in patients with neoplasms. Therefore, physicians should always be aware about the possibility of nephrotoxicity development.

Introduction: Drug-induced tubulointerstitial injury is a common cause of renal impairment. Since the mechanisms of drug-induced tubular injury are diverse, various treatment approaches are needed according to the pathogenesis. Renal biopsy is indispensable to determine not only the pathological diagnosis, but also the underlying mechanism, and to guide appropriate treatment. Most recently, one of the red yeast supplements has been widely highlighted as a novel cause of tubular damage, mainly in Japan and Asia. However, neither detailed pathological findings nor the mechanism of renal impairment has been sufficiently reported. Case Presentation: Two cases of renal impairment after taking red yeast supplement internally are presented. Both cases showed renal dysfunction with low uric acid, potassium, and phosphorus levels, characteristic features of Fanconi syndrome. The renal biopsy findings of both cases showed severe injury to the proximal tubules with mild inflammatory cell infiltration. The proximal tubules exhibited diffuse loss of the brush border, flattening, and tubular lumen dilation. Immunofluorescence showed no deposition of immunoglobulin and complement in the glomeruli and tubules. Electron microscopic findings indicated proximal tubular damage without crystal deposition. Moreover, immunohistochemistry using the proximal tubular marker CD10 and a marker for distal tubules including the loop of Henle, E-cadherin, collectively demonstrated that the focus of renal injury in both cases was mainly the proximal tubules. Conclusions: The red yeast rice supplement itself, its metabolized product, or other unknown contaminant components might directly induce proximal tubulopathy rather than an allergic reaction-related tubulointerstitial nephritis.

We present two cases of middle‐aged men who developed Fanconi syndrome and renal dysfunction after consuming "foods with functional claims (FFC)" containing red yeast rice. In the first case, the patient had consumed an FFC for 1 year and another FFC suspected to have contained nephrotoxin for 3 weeks; kidney biopsy performed during the acute phase of renal injury showed severe acute tubular necrosis and tubular cell regeneration. He achieved near‐complete recovery 40 days after the FFC was discontinued. In the second case, the patient had consumed FFC for 4 years and stopped 70 days prior to presentation; kidney biopsy revealed significant tubular recovery, persistent tubular injuries, and interstitial fibrosis. Although the manifestations of Fanconi syndrome subsided, mild renal dysfunction persisted. These cases suggest that FFC with nephrotoxins may induce Fanconi syndrome owing to acute tubular necrosis. Recovery is possible after discontinuing the FFC; while short‐term ingestion of FFC allows for tubular regeneration, its long‐term ingestion may cause irreversible damage and lead to chronic kidney disease. Long‐term follow‐up is crucial for preventing further renal deterioration. [ABSTRACT FROM AUTHOR]

Introduction Musculoskeletal injuries are one of the primary causes of Soldiers' inability to be medically ready, comprising over 80% of such causes. The electronic profile (e-Profile) is the way that musculoskeletal injuries are documented so that commanders will know the type of injury as well as the length of the time that the Soldier will need limited duty. A previous study of e-Profiles in an Army MTF Integrated Pain Management Center showed that the median length of an e-Profile was 30 days. It is in the best interest of the Army to have the Soldier out of the fight the minimum amount of time for recovery to ensure the unit readiness. The goal of this study was to utilize e-Profile data to see if a machine learning model can be developed to determine the appropriate time a Soldier needs to be on profile for a given diagnoses. Materials and Methods Institutional Review Board approval was obtained from the USAMRDC (protocol #M-10966). The initial dataset provided to the research team consisted of a single pipe delimited ("|") text file containing 2.9 million rows of e-Profile data. Linear regression, decision trees, and random forests (RFs) were evaluated to see which model would best predict the number of days needed for an e-Profile. Results Linear regression had an adjusted R-squared of 0.165. The positive predictive value of decision trees (0-to-30-day range of e-Profiles) was 73.6%, and the negative predictive value (30-90 days) was 60.9% with an area under the receiver operating characteristic curve (AUC) of 0.694 for the model. The positive predictive value of RFs was 85.3% (for the 0-30 range), and the negative predictive value was 58.7% (for the 30-90 range) with an AUC of 0.794. An AUC that approaches 1 indicates a more accurate prediction. Conclusions The 3 models (linear regression, decision trees, and RF) studied as part of this project did not predict the days on e-Profile with a high degree of certainty. Future research will focus on adding additional data to the e-Profile dataset in order to improve model accuracy. [ABSTRACT FROM AUTHOR]

Summary: Subtrochanteric femoral fracture is rare and intractable due to the possible association with low bone formation. Retrospective analysis of 38 patients with subtrochanteric femoral fractures revealed that four patients suffered from disorders related to low bone formation and there were specific treatments for two of them. Purpose: The main aim of this study was to detect latent metabolic bone diseases and skeletal dysplasia associated with low bone formation among patients with morphologic atypical femoral fracture (AFF). A second aim was to evaluate the frequency of recognized risk factors, such as antiresorptive agents, glucocorticoids, and age. Methods: Clinical information was retrospectively analyzed among 38 Japanese patients who were admitted to the Department of Orthopedic Surgery and Spinal Surgery and the Division of Emergency and Critical Care Medicine at the University of Tokyo Hospital with diagnoses of subtrochanteric fractures between February 2012 and March 2022. Results: Among 38 patients (including 30 females), 21 patients were aged 75 and over. Ten patients had past oral glucocorticoid use, and 18 had past antiresorptive agent use. Two patients were diagnosed with hypophosphatemic osteomalacia after the development of fractures. One patient was suspected to be a carrier of a loss-of-function variant of alkaline phosphatase, biomineralization associated (ALPL), and one other patient had previously been genetically diagnosed with pycnodysostosis. Among four patients with a diagnosis or suspicion of these metabolic bone diseases and skeletal dysplasia, four had past clinical fractures, two had past subtrochanteric femoral fractures, and two had subtrochanteric femoral fractures on both sides. Conclusion: If clinicians encounter patients with morphologic AFF, latent diseases related to low bone formation should be carefully differentiated because appropriate treatment may prevent delayed union and recurrent fractures. Additionally, it may be desirable to exclude these bone diseases in advance before initiating long-term use of antiresorptive agents in osteoporotic patients by screening with serum alkaline phosphatase levels to reduce the risk of morphologic AFF. [ABSTRACT FROM AUTHOR]

Background: Cystinosis is a lysosomal storage disorder characterized by an autosomal recessive phenotype. Intermediate cystinosis, which progresses slowly and causes renal failure, accounts for approximately 5% of all cystinosis cases. Patients with intermediate cystinosis may not exhibit the typical symptoms of cystinosis, such as Fanconi syndrome and ocular symptoms. Because of its diverse clinical presentation and rarity, intermediate cystinosis can be difficult to diagnose. Additionally, few patients can tolerate cystine-depleting drugs, such as cysteamine, because of their complicated administration schedules and side effects. We report a case of intermediate cystinosis that was treated with cysteamine for 10 years. Case presentation: Urinary abnormalities were first diagnosed when the patient was 3 years of age during a health examination specifically for 3-year-old children, which is unique to Japan. Cystinosis was diagnosed when the patient was 12 years of age. Cysteamine therapy was initiated and regular cystine concentration measurements were performed. Although proteinuria persisted, the patient's renal function progressed slowly. Two renal biopsies were performed, and multinucleated podocytes and cystine crystals without focal segmental glomerulosclerosis lesions were observed in the biopsy specimens. The patient's renal function remained stable. Conclusions: This case of intermediate cystinosis was treated with cysteamine over the course of 10 years. Intermediate cystinosis requires an appropriate diagnosis and long-term treatment. [ABSTRACT FROM AUTHOR]

Cystinosis is a rare autosomal recessive disease with an incidence 1 per 100,000–200,000 live births. It is caused by pathogenic variants of the cystinosin (CTNS) gene that lead to impaired cystine transport from lysosomes to cystosol, resulting in cystine accumulation in lysosomes and subsequent cellular dysfunction. The initial manifestation, cystine accumulation in proximal tubular cells (PTCs), causes renal Fanconi syndrome, which presents with proximal renal tubular acidosis and generalized dysfunction of the proximal tubule, including the presence of polyuria, glycosuria, phosphaturia, aminoaciduria, tubular proteinuria, growth retardation, and rickets. Eventually, glomerular involvement, glomerular proteinuria, focal segmental glomerulosclerosis (FSGS), and progression to kidney failure occur. Although the kidneys are the first organs affected, and play a key role in morbidity and mortality, extrarenal multiorgan involvement can occur in patients with cystinosis, which is seen not only in adults but in early ages in untreated patients, patients with insufficient treatment, and in those that don't comply with treatment. The treatment of cystinosis consists of supportive treatment for Fanconi syndrome, and specific lifelong cystine-depleting therapy using oral cysteamine. There is strong evidence that as early as possible, initiation and ongoing appropriate therapy with cysteamine are essential for delaying the progression to kidney failure, end-organ damage, and extrarenal involvement. The present review aimed to evaluate the extra renal complications of cystinosis. [ABSTRACT FROM AUTHOR]

This article examines the long-term kidney function of individuals with Lowe syndrome, a genetic disorder characterized by ocular disease, central nervous system disorder, and kidney disease. The study analyzed a large group of pediatric and adult patients with Lowe syndrome and found that all patients had congenital cataracts, CNS involvement, and Fanconi syndrome. The study also investigated the estimated glomerular filtration rate (eGFR) and clinical prognostic factors in these patients. The results indicate that kidney disease is a significant prognostic factor in Lowe syndrome, and further research is necessary to understand the progression of chronic kidney disease in adult patients with this syndrome. Another study analyzed the progression of chronic kidney disease (CKD) in individuals with Lowe syndrome, a rare genetic disorder. The study discovered that CKD progressed rapidly after the age of 10, with 84% of patients developing severe CKD after the age of 20. Nephrocalcinosis and hypercalciuria did not have a significant impact on kidney function. The study also found that age was the only factor significantly associated with kidney function. These findings suggest that the majority of individuals with Lowe syndrome develop end-stage kidney disease by their fourth decade of life. [Extracted from the article]

Objective: Several cases of Fanconi syndrome (FS), a severe form of nephrotoxicity, have been reported in patients with HIV on tenofovir-containing antiretroviral therapy. A systematic review of the published literature on tenofovir-related FS in patients with HIV was conducted. Data Sources: PubMed and Embase were queried to identify articles in English published between January 2005 and June 2023, reporting tenofovir-related FS in adults with HIV. Preclinical studies, conference/poster abstracts, commentaries and responses, and review papers were excluded. Study Selection and Data Extraction: Of the 256 articles screened, 57 met the inclusion criteria. These comprised 37 case reports, 11 case series, 1 cross-sectional study, 1 case-control study, 4 cohort studies, 1 single-arm open-label clinical trial, 1 sub-analysis of clinical trials, and 1 pooled analysis of clinical trials. Data Synthesis: Among 56 cases on which information was abstracted, median age at FS diagnosis was 50 years, 51.8% were men, and duration of tenofovir use ranged from 6 weeks to 11 years. Ritonavir was co-prescribed in almost half the cases. In observational and interventional studies, incidence of FS was low. Many studies reported resolution of FS symptoms after tenofovir discontinuation. All FS occurrences were identified in those on tenofovir disoproxil fumarate (TDF), except for one patient on tenofovir alafenamide (TAF). Relevance to Patient Care and Clinical Practice: Continuous monitoring of signs and symptoms of renal and bone toxicity is essential for patients with HIV on tenofovir-containing therapy. Conclusions: Occurrence of FS is low in patients with HIV treated with tenofovir-based regimens. Concomitant use of ritonavir may increase risk of FS. TAF may be a safer alternative than TDF in terms of nephrotoxicity. [ABSTRACT FROM AUTHOR]

Multiple myeloma commonly manifests with symptoms arising from the involvement of various organs, particularly the bone and kidneys. In this report, we detail the case of a 44-year-old man who was diagnosed with multiple myeloma associated with reduced bone density. He exhibited clinical findings of osteomalacia due to Fanconi syndrome (characterized clinically by bone pain and proximal weakness and biochemically by elevated serum alkaline phosphatase, hypophosphatemia, hypouricemia, and glucosuria). With phosphate replacement, there was a notable improvement in bone pain, osteomalacia, and bone mineral density. Nevertheless, the patient continued to experience renal wasting of phosphate, uric acid, and glucose despite achieving remission from multiple myeloma for nearly 2 years. Our case highlights several important clinical features of myeloma-associated Fanconi syndrome, including the need to recognize this complication to appropriately treat the underlying bone disease while avoiding osteoclast inhibitors and the long-term persistence of the proximal renal tubulopathy despite achieving remission from myeloma and correction of osteomalacia. [ABSTRACT FROM AUTHOR]

Purpose: Cryoglobulinemia is a pathological condition characterized by the presence of cryoglobulins in the blood, with cryoglobulinemic glomerulonephritis being the most frequent form of renal involvement. Fanconi syndrome presents as a generalized dysfunction of the proximal tubule, characterized by the presence of polyuria, phosphaturia, glycosuria, proteinuria, proximal renal tubular acidosis, and osteomalacia. We aimed to present five cases co-occurring with Fanconi syndrome and cryoglobulinemia. Methods: We retrospectively summarized the cases of five patients with Fanconi syndrome and cryoglobulinemia at Peking Union Medical College Hospital from January 2012 to June 2022. The clinical features, diagnosis, treatment, and prognosis were systematically analyzed. Results: All five patients exhibited typical features of Fanconi syndrome, and cryoglobulinemia was concurrently detected in all cases. These patients also exhibit positive anti-nuclear antibody spectrum and hyperglobulinemia, and IgM constitutes the predominant monoclonal component in cryoglobulins. In addition to supplemental treatment, timely immunosuppressive therapy may potentially benefit the long-term renal prognosis of patients with this condition. Conclusion: Our findings highlight the rare co-occurrence of Fanconi syndrome and cryoglobulinemia in clinical practice. Despite the lack of causal evidence, the coexistence of Fanconi syndrome and tubulointerstitial injury is also noteworthy in patients with cryoglobulinemia, underscoring the importance of thorough evaluation and tailored management in patients presenting with overlapping renal manifestations. Key Points • Patients with mixed cryoglobulinemia can clinically present with tubulointerstitial injury, specifically manifesting as Fanconi syndrome. • In addition to typical symptoms of Fanconi syndrome, these patients also exhibit positive anti-nuclear antibody spectrum and hyperglobulinemia, while IgM constitutes the monoclonal component in cryoglobulins. • Timely immunosuppressive therapy may improve long-term renal prognosis in these patients. [ABSTRACT FROM AUTHOR]

Objective: To review the current scientific literature on renal tubular acidosis (RTA) in people and small animals, focusing on diseases in veterinary medicine that result in secondary RTA. Data Sources: Scientific reviews and original research publications on people and small animals focusing on RTA. Summary: RTA is characterized by defective renal acid–base regulation that results in normal anion gap hyperchloremic metabolic acidosis. Renal acid–base regulation includes the reabsorption and regeneration of bicarbonate in the renal proximal tubule and collecting ducts and the process of ammoniagenesis. RTA occurs as a primary genetic disorder or secondary to disease conditions. Based on pathophysiology, RTA is classified as distal or type 1 RTA, proximal or type 2 RTA, type 3 RTA or carbonic anhydrase II mutation, and type 4 or hyperkalemic RTA. Fanconi syndrome comprises proximal RTA with additional defects in proximal tubular function. Extensive research elucidating the genetic basis of RTA in people exists. RTA is a genetic disorder in the Basenji breed of dogs, where the mutation is known. Secondary RTA in human and veterinary medicine is the sequela of diseases that include immune‐mediated, toxic, and infectious causes. Diagnosis and characterization of RTA include the measurement of urine pH and the evaluation of renal handling of substances that should affect acid or bicarbonate excretion. Conclusions: Commonality exists between human and veterinary medicine among the types of RTA. Many genetic defects causing primary RTA are identified in people, but those in companion animals other than in the Basenji are unknown. Critically ill veterinary patients are often admitted to the ICU for diseases associated with secondary RTA, or they may develop RTA while hospitalized. Recognition and treatment of RTA may reverse tubular dysfunction and promote recovery by correcting metabolic acidosis. [ABSTRACT FROM AUTHOR]

Numerous health concerns, primarily kidney injury, have been reported with the use of Beni-kōji CholesteHelp, a functional food containing red yeast rice. Here, we describe 2 cases of kidney injury caused by beni-kōji. The first case had normal kidney function before consuming the product. After several months of use, she developed hypertension. After 6 months of supplement consumption, her estimated glomerular filtration rate (eGFR) dropped to 22.5 mL/min/1.73 m2. A spot urine sample showed a urinary protein-to-creatinine ratio of 2.03 g/g, leading to the diagnosis of Fanconi syndrome. Kidney biopsy showed tubular degeneration. Thirty-five days after discontinuing the supplement, proteinuria resolved and the eGFR returned to baseline level. The second case, who had diabetes and normal kidney function, experienced severe kidney injury (eGFR, 3.5 mL/min/1.73 m2) after 4 months of Beni-kōji CholesteHelp use. He required hemodialysis for >2 weeks but recovered kidney function after the product was discontinued. Kidney biopsy showed tubular injury similar to the first case and glomeruli changes consistent with diabetic nephropathy. These cases indicate that beni-kōji use is associated with tubular toxicity. Further studies are required to identify the precise etiology and mechanism of kidney injury.

BackgroundThe exact mechanism of hyperammonemia is thought to be multifactorial, but is not yet fully understood. No studies have yet reported hyperammonemia combined with Fanconi syndrome caused by deferasirox.Case presentationA 10-year-old girl was admitted for vomiting and altered consciousness. Blood testing revealed hyperammonemia and normal liver and coagulation functions. During hospitalization, the patient also exhibited hyperchloremic metabolic acidosis, hypokalemia, hyponatremia, and hypophosphatemia. Additionally, urinalysis revealed glucose and protein levels clinically consistent with Fanconi syndrome. The patient had a history of severe beta-thalassemia and had received intermittent blood transfusions for approximately ten years. The patient had been administered oral deferasirox at a 400 mg/day dose at the age of four, which had been gradually increased to the current 750 mg/day dosage. Upon admission, deferasirox was discontinued and treatment including mechanical ventilation, continuous blood purification therapy for ammonia reduction and acidosis, and electrolyte imbalance corrections was administered. Subsequently, serological markers returned to normal, urine test findings improved. To the best of our knowledge, this is the first report of a case of hyperammonemia with Fanconi syndrome owing to deferasirox.ConclusionsFor effective management and long-term follow-up of chronic diseases in children, pediatricians must master standardized treatments and the adverse reactions of various drugs. When symptoms are difficult to explain clinically, we must trace the source and adjust the treatment plan to maximize improving the patient's prognosis.

Abstract Background Cystinosis, a rare autosomal recessive disease, stems from genetic alterations in the CTNS gene, leading to a malfunction of lysosomal ‘cystinosin’ protein. This dysfunction causes intracellular cystine accumulation, resulting in nephropathic and ocular abnormalities. Cystinosis is relatively rare in Asian countries, partly due to underreporting and lack of awareness, and cases often lack sufficient genetic evidence to support their diagnosis. This study presents a descriptive case series involving four Indian patients with cystinosis, elucidating clinical and genetic aspects. Methods All four patients underwent comprehensive ophthalmic evaluations. The corneal cystine crystal (CCC) score was determined using anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM). Genetic testing was performed using whole exome sequencing (WES). Results Corneal crystal deposition, a hallmark of cystinosis, was evident in all cases. Systemic analysis revealed manifestations such as polyuria, bony abnormalities, growth retardation, hypothyroidism, and developmental delay. Genetic testing in two patients identified a homozygous pathogenic variant c.18_21delGACT (p.Thr7PhefsX7) in the CTNS gene, previously reported to cause cystinosis in different ethnic populations. Conclusions Our case series sheds light on underrepresented cases of cystinosis in the Indian population. The rarity of this condition poses diagnostic challenges, leading to delayed or inaccurate diagnoses. AS-OCT can serve as a viable alternative to IVCM for assessing corneal crystal density status in cystinosis. Timely recognition and management are crucial in preventing complications, and the inclusion of genetic testing can expedite cystinosis diagnosis.

Background: Cystinosis, a rare autosomal recessive disease, stems from genetic alterations in the CTNS gene, leading to a malfunction of lysosomal 'cystinosin' protein. This dysfunction causes intracellular cystine accumulation, resulting in nephropathic and ocular abnormalities. Cystinosis is relatively rare in Asian countries, partly due to underreporting and lack of awareness, and cases often lack sufficient genetic evidence to support their diagnosis. This study presents a descriptive case series involving four Indian patients with cystinosis, elucidating clinical and genetic aspects. Methods: All four patients underwent comprehensive ophthalmic evaluations. The corneal cystine crystal (CCC) score was determined using anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM). Genetic testing was performed using whole exome sequencing (WES). Results: Corneal crystal deposition, a hallmark of cystinosis, was evident in all cases. Systemic analysis revealed manifestations such as polyuria, bony abnormalities, growth retardation, hypothyroidism, and developmental delay. Genetic testing in two patients identified a homozygous pathogenic variant c.18_21delGACT (p.Thr7PhefsX7) in the CTNS gene, previously reported to cause cystinosis in different ethnic populations. Conclusions: Our case series sheds light on underrepresented cases of cystinosis in the Indian population. The rarity of this condition poses diagnostic challenges, leading to delayed or inaccurate diagnoses. AS-OCT can serve as a viable alternative to IVCM for assessing corneal crystal density status in cystinosis. Timely recognition and management are crucial in preventing complications, and the inclusion of genetic testing can expedite cystinosis diagnosis. [ABSTRACT FROM AUTHOR]