ABSTRACT
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.
Subject(s)
Cystinosis , Fanconi Syndrome , Humans , Cystinosis/complications , Cystinosis/genetics , Fanconi Syndrome/etiology , Fanconi Syndrome/complications , Cysteamine/therapeutic use , Cystine Depleting Agents/therapeutic use , Amino Acid Transport Systems, Neutral/geneticsABSTRACT
Between April 2018 and August 2019, 6 dogs with laboratory diagnostic evidence of Fanconi syndrome were presented to the Tierklinik Hofheim. The presumptive diagnosis was confirmed via urine amino acid analysis in all dogs. In 5 of the 6 dogs an alimentary origin was suspected, in 3 dogs the course of the disease could be followed. Supportive therapeutic measures and elimination of jerky treats from the dogs' diet improved the clinical symptoms in all dogs with known follow-up. This is the first case series of dogs with alimentary acquired Fanconi syndrome in Germany. The frequency of occurrence of the disease in that short period of time in only one small animal clinic suggests a significantly higher incidence than currently assumed.
Subject(s)
Dog Diseases , Fanconi Syndrome , Pancytopenia , Animals , Diet , Dog Diseases/diagnosis , Dog Diseases/etiology , Dog Diseases/therapy , Dogs , Fanconi Syndrome/diagnosis , Fanconi Syndrome/etiology , Fanconi Syndrome/therapy , Fanconi Syndrome/veterinary , Germany , Pancytopenia/veterinaryABSTRACT
While nephropathic cystinosis is classically thought of as a childhood disease, with improved treatments, patients are more commonly living into adulthood. We performed a systematic review of the literature available on what complications this population faces as it ages. Nearly every organ system is affected in cystinosis, either from the disease itself or from sequelae of kidney transplantation. While cysteamine is known to delay the onset of end-stage kidney disease, its effects on other complications of cystinosis are less well determined. More common adult-onset complications include myopathy, diabetes, and hypothyroidism. Some less common complications, such as neurologic dysfunction, can still have a profound impact on those with cystinosis. Areas for further research in this area include additional study of the impact of cysteamine on the nonrenal manifestations of cystinosis, as well as possible avenues for new and novel treatments.
Subject(s)
Cystinosis , Adult , Cysteamine/therapeutic use , Cystinosis/complications , Cystinosis/drug therapy , Fanconi Syndrome/etiology , Humans , Kidney Failure, Chronic/etiology , Kidney Transplantation/adverse effectsABSTRACT
BACKGROUND: Chronic subclinical hemolysis is frequent in patients implanted with Left Ventricular Assist Device (LVAD) and is associated with adverse outcomes. Consequences of LVADs-induced subclinical hemolysis on kidney structure and function is currently unknown. METHODS: Thirty-three patients implanted with a Heartmate II LVAD (Abbott, Inc, Chicago IL) were retrospectively studied. Hemolysis, Acute Kidney Injury (AKI) and the evolution of estimated Glomerular Filtration Rate were analyzed. Proximal Tubulopathy (PT) groups were defined according to proteinuria, normoglycemic glycosuria, and electrolytic disorders. The Receiver Operating Characteristic (ROC) curve was used to analyze threshold of LDH values associated with PT. RESULTS: Median LDH between PT groups were statistically different, 688 IU/L [642-703] and 356 IU/L [320-494] in the "PT" and "no PT" groups, respectively p = 0.006. To determine PT group, LDH threshold > 600 IU/L was associated with a sensitivity of 85.7% (95% CI, 42.1-99.6) and a specificity of 84.6% (95% CI, 65.1-95.6). The ROC's Area Under Curve was 0.83 (95% CI, 0.68-0.98). In the "PT" group, patients had 4.2 [2.5-5.0] AKI episodes per year of exposure, versus 1.6 [0.4-3.7] in the "no PT" group, p = 0.03. A higher occurrence of AKI was associated with subsequent development of Chronic Kidney Disease (CKD) (p = 0.02) and death (p = 0.05). CONCLUSIONS: LVADs-induced subclinical hemolysis is associated with proximal tubular functional alterations, which in turn contribute to the occurrence of AKI and subsequent CKD. Owing to renal toxicity of hemolysis, measures to reduce subclinical hemolysis intensity as canula position or pump parameters should be systematically considered, as well as specific nephroprotective therapies.
Subject(s)
Acute Kidney Injury/physiopathology , Fanconi Syndrome/physiopathology , Heart Failure/physiopathology , Heart-Assist Devices/adverse effects , Acute Kidney Injury/blood , Acute Kidney Injury/etiology , Aged , Fanconi Syndrome/blood , Fanconi Syndrome/etiology , Female , Heart Failure/blood , Heart Failure/etiology , Hematologic Tests , Hemolysis/physiology , Humans , Kidney/metabolism , Kidney/physiopathology , Kidney Tubules, Proximal/pathology , L-Lactate Dehydrogenase/blood , Male , Middle Aged , Ventricular Dysfunction, Left/blood , Ventricular Dysfunction, Left/etiology , Ventricular Dysfunction, Left/physiopathologyABSTRACT
BACKGROUND: Renal abnormalities in HIV infected children may be due to the HIV infection or treatment among other factors. Tenofovir disoproxil fumarate (TDF) is associated with proximal renal tubular dysfunction, proteinuria and decrease in glomerular function. Studies in developed countries have shown variable prevalence of proximal renal tubular dysfunction in children on TDF. There are no known studies in developing countries, including Zimbabwe, documenting the proximal tubular function in HIV infected children on TDF. The aim of this study was to assess renal and proximal renal tubular function in HIV infected children receiving TDF and determine factors associated with proximal tubular dysfunction. METHODS: A descriptive cross-sectional study was conducted in HIV infected patients below 18 years of age attending outpatient clinics at two tertiary hospitals in Harare, who received a TDF-containing antiretroviral regimen for at least six months. Dipstick protein and glucose, serum and urine phosphate and creatinine levels were measured. Fractional excretion of phosphate was calculated. Estimated glomerular filtration rate (eGFR) was calculated using the Schwartz formula. Tubular dysfunction was defined by at least two of the following characteristics: normoglycaemic glycosuria, hypophosphatemia and fractional excretion of phosphate > 18%. FINDINGS: One hundred and ninety-eight children below 18 years of age were recruited over a period of six months. The prevalence of tubular dysfunction was 0.5%. Normoglycaemic glycosuria occurred in 1 (0.5%), fractional excretion of phosphate >18% in 4 (2%), and hypophosphatemia in 22 [11.1%] patients. Severe stunting was associated with increased risk of hypophosphatemia (OR 9.31 CI (1.18, 80.68) p = 0.03). Reduction in estimated glomerular filtration rate (eGFR) < 90ml/min/1.73m2 and proteinuria was evident in 35.9% and 32.8% of children, respectively. Concurrent TDF and HIV-1 protease inhibitor-based regimen was the only independent factor associated with reduction in GFR (OR 4.43 CI (1.32; 4.89) p = 0.016). CONCLUSION: Tubular dysfunction was uncommon in Zimbabwean children on a TDF-based ART regimen. Hypophosphatemia, proteinuria and reduction in eGFR were common. Reassessing renal function using more sensitive biomarkers is needed to examine the long-term tolerance of TDF.
Subject(s)
Anti-HIV Agents/therapeutic use , Fanconi Syndrome/etiology , HIV Infections/complications , Reverse Transcriptase Inhibitors/therapeutic use , Tenofovir/therapeutic use , Adolescent , Anti-HIV Agents/adverse effects , Child , Cross-Sectional Studies , Fanconi Syndrome/chemically induced , Female , Glomerular Filtration Rate , HIV Infections/drug therapy , Humans , Male , Proteinuria/etiology , Reverse Transcriptase Inhibitors/adverse effects , Tenofovir/adverse effects , Tertiary Care Centers , ZimbabweABSTRACT
CONTEXT: Children with nephropathic cystinosis (NC) show persistent hypophosphatemia, due to Fanconi syndrome, as well as mineral and bone disorders related to chronic kidney disease (CKD); however, systematic analyses are lacking. OBJECTIVE: To compare biochemical parameters of bone and mineral metabolism between children with NC and controls across all stages of CKD. DESIGN: Cross-sectional multicenter study. SETTING: Hospital clinics. PATIENTS: Forty-nine children with NC, 80 CKD controls of the same age and CKD stage. MAIN OUTCOME MEASURES: Fibroblast growth factor 23 (FGF23), soluble Klotho, bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRAP5b), sclerostin, osteoprotegerin (OPG), biochemical parameters related to mineral metabolism, and skeletal comorbidity. RESULTS: Despite Fanconi syndrome medication, NC patients showed an 11-fold increased risk of short stature, bone deformities, and/or requirement for skeletal surgery compared with CKD controls. This was associated with a higher frequency of risk factors such as hypophosphatemia, hypocalcemia, low parathyroid hormone (PTH), metabolic acidosis, and a specific CKD stage-dependent pattern of bone marker alterations. Pretransplant NC patients in mild to moderate CKD showed a delayed increase or lacked an increase in FGF23 and sclerostin, and increased BAP, TRAP5b, and OPG concentrations compared with CKD controls. Post-transplant, BAP and OPG returned to normal, TRAP5b further increased, whereas FGF23 and PTH were less elevated compared with CKD controls and associated with higher serum phosphate. CONCLUSIONS: Patients with NC show more severe skeletal comorbidity associated with distinct CKD stage-dependent alterations of bone metabolism than CKD controls, suggesting impaired mineralization and increased bone resorption, which is only partially normalized after renal transplantation.
Subject(s)
Bone Resorption/diagnosis , Chronic Kidney Disease-Mineral and Bone Disorder/diagnosis , Cystinosis/complications , Fanconi Syndrome/etiology , Renal Insufficiency, Chronic/etiology , Adolescent , Bone Resorption/etiology , Bone Resorption/physiopathology , Calcification, Physiologic/physiology , Child , Chronic Kidney Disease-Mineral and Bone Disorder/etiology , Chronic Kidney Disease-Mineral and Bone Disorder/physiopathology , Cross-Sectional Studies , Cystinosis/physiopathology , Cystinosis/surgery , Fanconi Syndrome/physiopathology , Fanconi Syndrome/surgery , Female , Fibroblast Growth Factor-23 , Humans , Kidney Transplantation , Male , Prospective Studies , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/physiopathology , Renal Insufficiency, Chronic/surgery , Severity of Illness IndexABSTRACT
A 49-year-old woman was admitted to hospital with intermittent dizziness and fatigue for 7 years. The symptoms were aggravated and accompanied by bone pain for more than 4 months. She was referred to our hospital. Laboratory tests and imaging findings suggested that acquired Fanconi Syndrome (FS) was associated with smoldering multiple myeloma (MM). Renal biopsy and electron microscopy confirmed the diagnosis of proximal light chain tubular disease (LCPT). LCPT causes proximal tubular dysfunction, which is characterized by the cytoplasmic crystal deposition usually kappa monoclonal light chain in the proximal tubule. MM with FS and LCPT is less common in clinical practice because it is difficult to diagnose. This is a typical case focusing on the differential diagnosis of monoclonal gammopathy of renal significance(MGRS) such as LCPT and plasma cells diseases.
Subject(s)
Anemia , Dizziness/etiology , Fanconi Syndrome/etiology , Fatigue/etiology , Kidney Diseases/complications , Multiple Myeloma , Paraproteinemias/complications , Proteinuria , Fanconi Syndrome/diagnosis , Female , Humans , Immunoglobulin kappa-Chains , Kidney Diseases/diagnosis , Middle Aged , Paraproteinemias/diagnosisABSTRACT
ANTECEDENTES Y OBJETIVOS: La cistinosis es un error innato del metabolismo cuyas características clínicas incluyen compromiso renal severo y formación de cristales de cistina en la córnea, especialmente en la presentación adulta de la enfermedad. Es una enfermedad tratable, por lo cual establecer el diagnóstico de forma oportuna es fundamental para iniciar la terapia. Para la confirmación bioquímica de la enfermedad se requiere determinar las concentraciones intracelulares de cistina, para lo cual se han reportado diferentes métodos tanto para el aislamiento de las células como para la cuantificación del aminoácido. Con el objetivo de mejorar el diagnóstico bioquímico confirmatorio en nuestro medio establecimos un protocolo de cuantificación intraleucocitaria de cistina. MÉTODOS: Se implementó un método de cuantificación de cistina en polimorfonucleares por cromatografía líquida de alta resolución, evaluando el mejor anticoagulante a utilizar, la estabilidad de la muestra a 4̊ C y estableciendo valores de referencia para nuestra población. RESULTADOS: Se determinó que la muestra para cuantificación intraleucocitaria de cistina debe ser anticoagulada mediante la adición de ácido cítrico-dextrosa como anticoagulante. La muestra debe ser procesada inmediatamente, dada su baja estabilidad incluso en refrigeración. Con 50 individuos sanos se estableció como punto de corte para nuestra población 0,34 nmol 1/2 cistina/mg. CONCLUSIÓN: La adaptación realizada del método de cuantificación de cistina utiliza el número más alto de muestras control hasta ahora reportado en la literatura. Nuestros resultados dan cuenta de la necesidad de implementar el método a nivel local y reafirman la conveniencia de que cada laboratorio establezca sus propios valores de referencia para proporcionar una mayor confiabilidad a la hora de interpretar los resultados
Background and aims: Cystinosis is an inborn error of metabolism, clinically characterised by severe renal involvement and development of corneal cystine deposits, especially in the adult form of the disease. Cystinosis is a treatable condition. Therefore, an early diagnosis is necessary to start therapy. For biochemical confirmation of the condition it is necessary to quantify intracellular cystine concentrations. For this, different methods have been described with variations in cell isolation strategies and the amino acid quantification techniques used. In order to improve confirmatory biochemical diagnosis in our setting, a protocol for intraleukocitary cystine quantification was established. METHODS: A high performance liquid chromatography based method for cystine quantification in polymorphonuclear cells was implemented. Evaluation of the best anticoagulant to use and temperature stability of the sample at 4̊C were performed. In addition, we established reference values for our population. RESULTS: It was determined that intraleukocitary cystine quantification must be performed in blood samples containing acid-citrate-dextrose as anticoagulant. Samples must be processed immediately due to their poor stability even when refrigerated. Based on the results from 50 healthy individuals, the cut-off point established for our population was 0.34 nmol 1/2 cystine/mg. CONCLUSION: The adaptation performed to the cystine quantification method here presented the highest control population that has been reported in the literature so far. Our results highlight the need for making available a cystine quantification method locally and confirm the convenience for each laboratory to establish its own reference values to provide greater reliability for interpreting results
Subject(s)
Humans , Cystine/blood , Cystinosis/diagnosis , Neutrophils/chemistry , Anticoagulants , Chromatography, High Pressure Liquid , Citric Acid , Cold Temperature , Colombia , Fanconi Syndrome/etiology , Glucose/analogs & derivatives , Reference ValuesABSTRACT
BACKGROUND AND AIMS: Cystinosis is an inborn error of metabolism, clinically characterised by severe renal involvement and development of corneal cystine deposits, especially in the adult form of the disease. Cystinosis is a treatable condition. Therefore, an early diagnosis is necessary to start therapy. For biochemical confirmation of the condition it is necessary to quantify intracellular cystine concentrations. For this, different methods have been described with variations in cell isolation strategies and the amino acid quantification techniques used. In order to improve confirmatory biochemical diagnosis in our setting, a protocol for intraleukocitary cystine quantification was established. METHODS: A high performance liquid chromatography based method for cystine quantification in polymorphonuclear cells was implemented. Evaluation of the best anticoagulant to use and temperature stability of the sample at 4ÌC were performed. In addition, we established reference values for our population. RESULTS: It was determined that intraleukocitary cystine quantification must be performed in blood samples containing acid-citrate-dextrose as anticoagulant. Samples must be processed immediately due to their poor stability even when refrigerated. Based on the results from 50 healthy individuals, the cut-off point established for our population was 0.34nmol 1/2 cystine/mg. CONCLUSION: The adaptation performed to the cystine quantification method here presented the highest control population that has been reported in the literature so far. Our results highlight the need for making available a cystine quantification method locally and confirm the convenience for each laboratory to establish its own reference values to provide greater reliability for interpreting results.
Subject(s)
Cystine/blood , Cystinosis/diagnosis , Neutrophils/chemistry , Anticoagulants , Chromatography, High Pressure Liquid , Citric Acid , Cold Temperature , Colombia , Fanconi Syndrome/etiology , Glucose/analogs & derivatives , Humans , Reference ValuesABSTRACT
We describe a boy who presented with neonatal hypotonia, followed by delayed motor development and growth impairment. Further evaluation revealed rickets caused by proximal renal tubular dysfunction. At age 3, the boy exhibited dysmorphic features and bilateral cataract. Genetic analysis of the OCRL gene showed a novel variant in exon 13: c.1250T>A, p.Val417Asp; in silico and segregation analysis confirmed the variant to be pathogenic, compatible with the diagnosis of the oculocerebrorenal syndrome of Lowe. Lowe syndrome is a rare multisystemic disorder; the diagnostic triad requires involvement of the eye, central nervous system and the proximal renal tubule. Typical clinical features are congenital cataract, glaucoma, hypotonia, mental and behavioral problems, benign skin lesions, platelet dysfunction and dental abnormalities. Phenotypic features early in life may be nonspecific, which is illustrated by this case with a late manifestation of cataract. Because an early diagnosis can lead to better counseling and treatment, we suggest urinary testing for proteinuria as a part of the evaluation of children with unexplained hypotonia.
Subject(s)
Muscle Hypotonia , Oculocerebrorenal Syndrome , Phosphoric Monoester Hydrolases/genetics , Cataract/diagnosis , Cataract/etiology , Child, Preschool , Developmental Disabilities/diagnosis , Developmental Disabilities/etiology , Early Diagnosis , Early Medical Intervention , Fanconi Syndrome/diagnosis , Fanconi Syndrome/etiology , Genetic Testing/methods , Humans , Male , Motor Disorders/diagnosis , Motor Disorders/etiology , Muscle Hypotonia/diagnosis , Muscle Hypotonia/genetics , Muscle Hypotonia/urine , Mutation , Oculocerebrorenal Syndrome/diagnosis , Oculocerebrorenal Syndrome/genetics , Oculocerebrorenal Syndrome/physiopathologySubject(s)
Fanconi Syndrome/diagnosis , Fanconi Syndrome/etiology , Lenalidomide/adverse effects , Aged , Biomarkers , Female , Humans , Kidney Tubules, Proximal/drug effects , Kidney Tubules, Proximal/pathology , Lenalidomide/administration & dosage , Lenalidomide/therapeutic use , Middle Aged , Multiple Myeloma/complications , Multiple Myeloma/diagnosis , Multiple Myeloma/drug therapyABSTRACT
RATIONALE: Renal Fanconi syndrome (FS) is a rare complication of monoclonal gammopathy. It is characterized by the impairment of renal proximal tubular function leading to normoglycemic glycosuria, aminoaciduria, hypophosphatemia, hypouricemia and proximal renal tubular acidosis. Renal impairment in monoclonal gammopathy, without fulfilling the criteria of multiple myeloma, is categorized as monoclonal gammopathy of renal significance (MGRS). PATIENT CONCERNS: A 54-year-old male presented with progressively aggravated bone pain and limitation of activity was admitted to our department. A proximal renal tubular damage was suggested by hypophosphatemia, compensated metabolic acidosis, renal glycosuria, aminoaciduria, and hypouricemia. M-protein of IgA kappa was detected by immunofixation electrophoresis. Mildly increased plasma cells were found in bone marrow cytomorphologic examination. Renal biopsy revealed diffuse linear monoclonal IgA-kappa light chain deposits along tubular basement membranes (TBMs), while lambda was negative. Electron microscopy showed granular electron-dense deposits along the outer aspect of TBMs. DIAGNOSES: The patient was diagnosed as FS induced osteomalacia secondary to monoclonal gammopathy of renal significance (MGRS) (IgA-κ type) and LCDD. INTERVENTIONS: He was treated with bortezomib, supplementation by phosphate, alkali agents, and active vitamin D. He responded well to the treatment symptomatically. OUTCOMES: We reported a rare case of adult acquired FS with hypophosphatemic osteomalacia secondary to LCDD associated with MGRS and the patient was successfully treated with bortezomib. LESSONS: Although few cases of LCDD with isolated symptoms of tubulointerstitial nephropathy, rather than glomerular symptoms have been reported. It still needs to be recognized as a differential diagnosis in monoclonal gammopathy.
Subject(s)
Fanconi Syndrome/etiology , Immunoglobulin kappa-Chains/analysis , Kidney Diseases/complications , Paraproteinemias/complications , Diagnosis, Differential , Fanconi Syndrome/diagnosis , Fanconi Syndrome/drug therapy , Fanconi Syndrome/pathology , Humans , Kidney Diseases/diagnosis , Kidney Diseases/drug therapy , Kidney Diseases/pathology , Male , Middle Aged , Paraproteinemias/diagnosis , Paraproteinemias/drug therapy , Paraproteinemias/pathologyABSTRACT
Proximal renal tubular acidosis (pRTA) is an inherited or acquired clinical syndrome in which there is a decreased bicarbonate reclamation in the proximal tubule resulting in normal anion gap hyperchloremic metabolic acidosis. In children, pRTA may be isolated but is often associated with a general proximal tubular dysfunction known as Fanconi syndrome which frequently heralds an underlying systemic disorder from which it arises. When accompanied by Fanconi syndrome, pRTA is characterized by additional renal wasting of phosphate, glucose, uric acid, and amino acids. The most common cause of inherited Fanconi syndrome in the pediatric age group is cystinosis, a disease with therapeutic implications. In this article, we summarize the clinical presentation and differential diagnosis of pRTA and Fanconi syndrome and provide a practical approach to their evaluation in children.
Subject(s)
Acidosis, Renal Tubular/diagnosis , Acidosis, Renal Tubular/etiology , Fanconi Syndrome/etiology , Acidosis, Renal Tubular/drug therapy , Acidosis, Renal Tubular/genetics , Child , Cystinosis/complications , Dent Disease/complications , Fanconi Syndrome/drug therapy , Fanconi Syndrome/genetics , Humans , Kidney Tubules, Proximal , Oculocerebrorenal Syndrome/complicationsABSTRACT
Legionella pneumonia is occasionally accompanied by renal complications; however, the cause of this remains unknown. We herein report a 70-year-old Japanese man with Legionella pneumonia who presented with hyponatremia, hypophosphatemia, and hypouricemia. The levels of urinary ß2-microglobulin and N-acetyl-ß-D-glucosaminidase were remarkably high, indicating severe renal tubular damage. The presence of glycosuria and aminoaciduria as well as increased fractional excretion of uric acid and decreased tubular reabsorption of phosphate indicated that the patient's condition was complicated with Fanconi syndrome. After antimicrobial therapy, the electrolyte abnormalities and renal tubular damage were completely resolved.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Fanconi Syndrome/etiology , Hyponatremia/complications , Hypophosphatemia/complications , Legionnaires' Disease/complications , Legionnaires' Disease/drug therapy , Pneumonia/complications , Aged , Asian People , Humans , Male , Treatment OutcomeABSTRACT
This article presents a case of cystinosis in a young man. Diagnosis of the disease and the problem of transition to adult care are described. Cystinosis is a rare lysosomal storage disease with first manifestation in early childhood presenting as renal Fanconi syndrome. Without treatment, the disease leads to severe health impairment. Due to the rarity of the disease, a correct diagnosis is often delayed. Without treatment, cystinosis often leads to end-stage renal failure, blindness, hypothyroidism, diabetes mellitus, and rickets. Cystine-depleting therapy with cysteamine significantly improves mortality and quality of life.
Subject(s)
Cysteamine/therapeutic use , Cystine Depleting Agents/therapeutic use , Cystine/blood , Cystine/metabolism , Cystinosis/diagnosis , Cystinosis/drug therapy , Fanconi Syndrome/drug therapy , Adult , Child , Child, Preschool , Cysteamine/administration & dosage , Cystine Depleting Agents/administration & dosage , Fanconi Syndrome/diagnosis , Fanconi Syndrome/etiology , Humans , Kidney/pathology , Lysosomes/metabolism , Male , Quality of LifeABSTRACT
We herein report two cases of Fanconi syndrome with refractory hypophosphatemic osteomalacia that was difficult to correct by phosphorus replacement therapy. The pathological result was a bony giant cell tumor and osteosarcoma, respectively. Interestingly, after resection of the tumors, the patient with osteosarcoma recovered completely but the patient with the bony giant cell tumor had a relapse. Although she underwent nine operations, her symptoms and laboratory tests did not improve. These findings indicate that Fanconi syndrome can result from a bone tumor.
Subject(s)
Bone Neoplasms/complications , Fanconi Syndrome/etiology , Giant Cell Tumor of Bone/complications , Osteosarcoma/complications , Adult , Child , Fanconi Syndrome/drug therapy , Female , Humans , Hypophosphatemia/drug therapy , Hypophosphatemia/etiology , Osteomalacia/drug therapy , Osteomalacia/etiology , Phosphorus Compounds/administration & dosageABSTRACT
Fanconi syndrome is a dysfunction of the proximal renal tubules that results in impaired reabsorption and increased urinary loss of phosphate and other solutes. The pathophysiology of drug-induced Fanconi syndrome is unclear. Here we report the case of a 36-year-old woman who presented with pain in multiple bones and proteinuria. She had a 7-year history of taking adefovir at 10 mg/day for chronic hepatitis B. Three years previously she had received surgery for a nontraumatic right femur neck fracture, after which she continued to complain of pain in multiple bones, and proteinuria, glycosuria, and phosphaturia were noted. The findings of a light-microscope examination of a renal biopsy sample were normal, but mitochondrial damage of the proximal tubules was evident in electron microscopy. Western blot analysis revealed that the level of serum fibroblast growth factor 23 (FGF23) was lower than in normal controls. After 2 months of treatment, hypophosphatemia and proximal tubular dysfunction were reversed, and serum FGF23 had normalized. This case suggests that direct mitochondrial damage in proximal tubules can cause drug-induced Fanconi syndrome associated with osteomalacia.
Subject(s)
Adenine/analogs & derivatives , Fanconi Syndrome/diagnosis , Organophosphonates/adverse effects , Osteomalacia/diagnosis , Adenine/adverse effects , Adenine/therapeutic use , Adenine/toxicity , Adult , Bone and Bones/drug effects , Fanconi Syndrome/etiology , Female , Fibroblast Growth Factor-23 , Fibroblast Growth Factors/blood , Hepatitis B/drug therapy , Humans , Hypophosphatemia/etiology , Hypophosphatemia/pathology , Kidney Tubules, Proximal/pathology , Mitochondria/drug effects , Mitochondria/pathology , Organophosphonates/therapeutic use , Organophosphonates/toxicity , Osteomalacia/etiologySubject(s)
Diet, Reducing/methods , Fanconi Syndrome , Kidney Tubules, Proximal , Poultry , Roxarsone/toxicity , Animals , Anti-Bacterial Agents/toxicity , Arsenic/urine , Diagnosis, Differential , Dietary Proteins , Fanconi Syndrome/blood , Fanconi Syndrome/diagnosis , Fanconi Syndrome/etiology , Female , Humans , Kidney Function Tests/methods , Kidney Tubules, Proximal/drug effects , Kidney Tubules, Proximal/pathology , Kidney Tubules, Proximal/physiopathology , Middle Aged , Obesity/diet therapy , Patient Care Management/methods , Treatment OutcomeABSTRACT
We describe the case of a 50-year-old woman presenting to our acute medicine department with generalised non-specific symptoms on a background of HIV managed on triple therapy (tenofovir, lamivudine and zidovudine). On admission, she was noted to be acidotic with proteinuria, glycosuria, hypophosphataemia and generalised body pain, and was diagnosed with Fanconi's renotubular syndrome secondary to tenofovir. It was also noted that she had elevated liver dysfunction markers, and an MRI of the liver revealed a focal stricture near the ampulla of Vater, resulting in a diagnosis of AIDS cholangiopathy. These two diagnoses are rare complications of HIV, and the presence of both these pathologies in a single patient has never been reported in the literature before, and we therefore believe that this case is the first of its kind.
Subject(s)
Cholangitis/etiology , Fanconi Syndrome/etiology , HIV Infections/complications , Acquired Immunodeficiency Syndrome/etiology , Anti-HIV Agents/therapeutic use , Female , HIV Infections/drug therapy , Humans , Lamivudine/therapeutic use , Middle Aged , Tenofovir/therapeutic use , Zidovudine/therapeutic useABSTRACT
We report a 40-year-old man who presented with multiple bone pseudofractures after about 20 years from the onset of Wilson's disease (WD). At age 36, he first noticed pain in his left shoulder. At age 39, he had multiple chest pain. On neurologic examinations, dysarthria and dysphagia due to pseudobulbar palsy, rigidity and tremor on right upper lim were observed. WD was confirmed because of low levels of plasma cupper and ceruloplasmin in addition to ATP7B gene mutation. The chest X-ray revealed multiple fractures of the several ribs. We diagnosed osteomalacia due to Fanconi's syndrome because of hypophosphatemia and the impairment of renal tubules for WD. After administration of vitamin D, there happened no new bone pseudofractures. Although bone pseudofractures accompanied by Wilson's disease generally happen in childhood, we should be aware of this symptom even in adulthood.