The Fanconi syndrome

Abstract

It is now customary to refer to the triad of the skeletal lesions of hypophosphatemia (rickets or osteomalacia), renal aminoaciduria, and renal glycosuria as the Fanconi syndrome. This combination of physiologic disturbances results from impairment of renal tubule mechanisms which are concerned with tubular reabsorption of phosphate, amino acids, and glucose. Other renal tubular systems may also be affected so that hyperchloremic acidosis, hypokalemia, and polyuria may be associated with the main triad. The Fanconi syndrome can probably result from injury of renal tubule cells by a wide variety of agents. These may be of endogenous origin due to hereditary metabolic disorders or may be exogenous toxic substances. Cystine storage disease which is an hereditary disturbance transmitted by a recessive gene is the most common cause of the Fanconi syndrome in infancy and early childhood. The Fanconi syndrome in late childhood and adult life is usually not hereditary and may be of diverse pathogenesis. Heavy metal poisoning and multiple myeloma are among the possible etiologic factors of the Fanconi syndrome but in most instances the mechanism of the renal tubule injury is unknown. The disturbance of regulation of serum phosphate levels in the Fanconi syndrome can be overcome by large amounts of vitamin D so that the hypophosphatemia can be corrected and more normal calcification and growth of the rachitic or osteomalacic bone can be achieved. In some instances, the other renal tubular dysfunctions are also ameliorated by vitamin D therapy so that the aminoaciduria is lessened and the chronic acidosis is improved. Studies of amino acid excretion in the urine should be made in all cases of refractory rickets or osteomalacia if the problem is to be accurately classified since marked generalized aminoaciduria is one of the constant diagnostic characteristics of the Fanconi syndrome.