Orthopedics - Oleksa A.P. 2006

Pathophysiology of Joints
Developmental Defects and Congenital Skeletal Anomalies
Fanconi Syndrome

Fanconi syndrome is a form of Renal osteodystrophy first described by Fanconi in 1931, and subsequently by De Toni in 1933 and Debré in 1934.

A distinction should be made between Primary and secondary Fanconi syndromes.

Primary Fanconi syndrome is inherited in an autosomal recessive manner (Dent C.E., Harris C.M., 1952; Harrison H., 1958; Ben-Ishay D., 1961).

Secondary Fanconi syndrome has been reported in association with nephrosclerosis, heavy metal poisoning, and other conditions.

Although Fanconi syndrome also exhibits vitamin D resistance, it differs from typical renal Rickets by a specific set of morphological, functional, and biochemical features.

While renal rickets involves damage to both the tubular and glomerular apparatus of the Kidneys—leading to the retention in Blood serum of phosphates and other waste products that are normally excreted in the urine—Fanconi syndrome exclusively affects the tubular system, resulting in impaired tubular reabsorption. This syndrome causes excessive urinary loss of Amino Acids, glucose, calcium, phosphorus, sodium, potassium, and other substances. Similar to renal rickets, acidosis is present; however, Aminoaciduria is a mandatory diagnostic symptom of Fanconi syndrome, along with hypophosphatemia in the blood serum.

Cystine accumulates in the body of an affected child, and its crystals may deposit in the cornea, Lymph Nodes, and Bone Marrow.

Clinically, Fanconi syndrome manifests as stunted growth and skeletal abnormalities. Although radiological Changes in the bones are largely similar to those seen in renal osteopathy, Fanconi syndrome is characterized by severe bone softening, which inevitably leads to skeletal deformities—particularly of the lower extremities—as the child grows. Affected individuals, typically male adolescents or young adults, present with pain in the pelvis, spine, or long bones, accompanied by Muscle weakness.

Consequently, bone pathology is driven by: 1) impaired phosphate reabsorption leading to secondary hypophosphatemia; 2) increased urinary calcium excretion; 3) acidosis; and 4) secondary hyperparathyroidism, which accelerates bone mineral resorption to maintain serum calcium levels, although De Seze S. et al. (1964) did not observe parathyroid hyperfunction in their clinical studies of patients with Fanconi syndrome.

Treatment. Management of Fanconi syndrome primarily focuses on correcting acidosis, followed by restoring Calcium and phosphorus balance.

Dialysis is most commonly used to correct acidosis. Once acidosis is resolved, patients are prescribed high doses of vitamin D under strict monitoring of 24-hour urinary calcium excretion and serum calcium levels. Calcium supplements are avoided to prevent nephrocalcinosis.