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