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Very rare, X-linked, inherited disorder characterized by onset in childhood or adulthood, tubular proteinuria hypercalciuria, calcium nephrolithiasis, nephrocalcinosis, and chronic renal failure.

Renal Fanconi Syndrome with Nephrocalcinosis and Renal Stones; Nephrolithiasis, X-Linked Recessive, Type II; Nephrolithiasis II.

Genetic disorder first described by C.E. Dent and M. Friedman in 1964.

X-linked recessive inheritance.

Generalized transport dysfunction of the proximal renal tubule caused by mutation in the CLCN5 chloride channel gene (gene map locus at Xp11.22), leading to impaired reabsorption of amino acids, glucose, calcium, phosphate, bicarbonate, magnesium, sodium, potassium, water, uric acid, and lowmolecular-weight proteins. Urinary losses can lead to polyuria, polydipsia, dehydration, hypokalemia, metabolic acidosis, and hypophosphatemia. The second component of the syndrome is a vitamin D-resistant metabolic bone disease that is responsible for rickets in children and osteomalacia in adults.

Clinically evocated in males presenting with Fanconi syndrome and nephrocalcinosis or renal stones.

Clinical manifestations are related to the underlying disease. In the pediatric population, failure to thrive results from chronic acidosis, dehydration, hypokalemia, hypophosphatemia, and vitamin D-resistant rickets. Urinalysis reveals hypercalciuria, phosphaturia, microglobulinuria, particularly β2-microglobulin, α1-microglobulin, and retinol-binding protein. Microglobulinuria is seen in asymptomatic female heterozygotes. Plasma amino acids levels are normal because urinary losses are minimal compared to amino acid intake. Hyperchloremic metabolic acidosis with normal anion gap is usually moderate. When it increases in severity, urinary pH decreases. Hyponatremia, hypophosphatemia, and occasionally hypouricemia may occur. Renal biopsy reveals a “swan-neck” deformity of the proximal convoluted tubule.

Obtain renal function tests (sodium, potassium, calcium, phosphate blood levels); urinalysis; creatinine clearance test if creatinine blood level is increased; request nephrology consultation if necessary. Obtain arterial blood gases (hyperchloremic nonanion gap metabolic acidosis), blood cell count, and hemoglobin level (anemia). Evaluate cardiac function by ECG for arrhythmias resulting from electrolyte abnormalities. Further testing, such as echocardiography, and radionuclide imaging, when necessary, may reveal decreased cardiac function secondary to uremia. Elective surgery should not be performed before optimization of acid-base and fluid-electrolyte status.

Metabolic acidosis with bicarbonate loss and sodium/potassium wasting is treated with administration of intravenous fluids having bicarbonate and electrolyte supplements. Under general anesthesia, mild intraoperative hyperventilation contributes to improvement of acid-base status. In cases where large volume shifts are expected, a central venous pressure line, a pulmonary arterial catheter in the presence of end-stage renal failure with cardiac dysfunction, or transesophageal echocardiography may facilitate volume management and assessment of ventricular function. An arterial line is required for close follow-up of blood gases, electrolytes, and blood pressure variations. Monitor urine output. Patients with rickets or osteomalacia should be carefully positioned and padded. Although renal Fanconi syndrome is different from Fanconi pancytopenia, anemia and coagulopathy may result as a consequence of end-stage renal failure.

Avoid nephrotoxic drugs (e.g.: tetracyclines, aminoglycosides). When renal function is decreased, titrate carefully all anesthetic agents eliminated by the kidney.

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