Fanconi Syndrome

Fanconi syndrome is caused by a complex dysfunction in the proximal tubule affecting the reabsorption of amino acids, glucose, phosphates, sometimes HCO3−, uric acid, citrates, low-molecular-weight proteins, magnesium, calcium, potassium, and water. It can be primary (congenital), as in the case of cystinosis, or secondary (acquired), after poisoning with heavy metals (lead, cadmium, mercury), in monoclonal gammopathy of renal significance (MGRS), multiple myeloma, polycystic kidney disease, nephrotic syndrome, tubulointerstitial nephritis, and after kidney transplant.

The signs and symptoms develop as a consequence of the renal loss of phosphate, HCO3−, potassium, and water. Hypophosphatemia, proximal renal tubular acidosis (pRTA), and the concomitant abnormal vitamin D metabolism impair growth in children and can lead to rickets or osteomalacia resistant to vitamin D doses that are effective in usual rickets. The loss of potassium in urine is a consequence of increased aldosterone secretion due to decreased sodium reabsorption in the proximal tubule. A vasopressin-resistant secondary urinary concentrating defect causes polyuria and polydipsia. Aminoaciduria and glycosuria rarely cause symptoms. The presenting symptoms of Fanconi syndrome in adults may be general weakness, polyuria, bone pain and deformities, sometimes pathologic fractures, decreased muscle tone progressing to flaccid paralysis in patients with severe potassium deficiency.

Diagnosis: Simultaneous aminoaciduria, hyperphosphaturia, glycosuria, and often pRTA. Radiographs show features of rickets, osteomalacia, and pathologic fractures. The causes of secondary damage to the proximal tubule should be investigated.

Treatment: Treatment is symptomatic and consists of correcting disturbances to achieve homeostasis. In hypophosphatemia use oral phosphorus (≥0.5 to 3.0 g/d of elemental phosphorus in 4-6 doses: see Phosphate Disturbances). Use biologically active vitamin D metabolites or analogues. During treatment monitor the patient’s serum and urine calcium concentration (avoid hypercalcemia and hypercalciuria); in the case of acidosis use bicarbonates in the treatment of pRTA: see Proximal (Type 2) Renal Tubular Acidosis (pRTA); supplement potassium to correct potassium deficiency.

In secondary Fanconi syndrome effective treatment consists of treating the underlying cause or disease.