Fanconi syndrome consists of multiple defects in renal proximal tubular reabsorption, causing glucosuria, phosphaturia, generalized aminoaciduria, and bicarbonate wasting. It may be hereditary or acquired. Symptoms in children are failure to thrive, growth retardation, and rickets. Symptoms in adults are osteomalacia and muscle weakness. Diagnosis is by showing glucosuria, phosphaturia, and aminoaciduria. Treatment is sometimes bicarbonate and potassium replacement, removal of offending nephrotoxins, and measures directed at renal failure.
Etiology of Fanconi Syndrome
Fanconi syndrome can be
Hereditary
Acquired
Hereditary Fanconi syndrome
This disorder usually accompanies another genetic disorder, particularly cystinosis. Cystinosis is an inherited (autosomal recessive) metabolic disorder in which cystine accumulates within cells and tissues (and is not excreted to excess in the urine as occurs in cystinuria). Besides renal tubular dysfunction, other complications of cystinosis include eye disorders, hepatomegaly, hypothyroidism, and other manifestations.
Fanconi syndrome may also accompany Wilson disease, hereditary fructose intolerance, galactosemia, oculocerebrorenal syndrome (Lowe syndrome), mitochondrial cytopathies, and tyrosinemia. Inheritance patterns vary with the associated disorder.
Acquired Fanconi syndrome
multiple myeloma, amyloidosis, intoxication with heavy metals or other chemicals, or .
Pathophysiology of Fanconi Syndrome
Various defects of proximal tubular transport function occur, including impaired resorption of glucose, phosphate, amino acids, bicarbonate, uric acid, water, potassium, and sodium. The aminoaciduria is generalized and, unlike that in cystinuria, increased cystine excretion is a minor component.
The basic pathophysiologic abnormality is unknown but may involve a mitochondrial disturbance. Low levels of serum phosphate cause rickets, which is worsened by decreased proximal tubular conversion of vitamin D to its active form.
Symptoms and Signs of Fanconi Syndrome
In hereditary Fanconi syndrome, the chief clinical features—proximal tubular acidosis, hypophosphatemic rickets, hypokalemia, polyuria, and polydipsia—usually appear in infancy.
When Fanconi syndrome occurs because of cystinosis, failure to thrive and growth retardation are common. The retinas show patchy depigmentation. Interstitial nephritis develops, leading to progressive renal failure that may be fatal before adolescence.
In acquired Fanconi syndrome, adults present with the laboratory abnormalities of renal tubular acidosis (proximal type 2—see table Some Features of Different Types of Renal Tubular Acidosis), hypophosphatemia, and hypokalemia. They may present with symptoms of bone disease (osteomalacia) and muscle weakness.
Diagnosis of Fanconi Syndrome
Urine testing for glucose, phosphates, and amino acids
Diagnosis is made by showing the abnormalities of renal function, particularly glucosuria (in the presence of normal serum glucose), phosphaturia, and aminoaciduria. In cystinosis, slit-lamp examination may show cystine crystals in the cornea.
Treatment of Fanconi Syndrome
Sometimes potassium supplementation
Other than removing the offending nephrotoxin, there is no specific treatment.
Early diagnosis and treatment in children can improve height prognosis (1, 2).
Potassium depletion may require replacement therapy with a potassium-containing salt.
Hypophosphatemic rickets can be treated.
Kidney transplantation has been successful in treating renal failure. However, when cystinosis is the underlying disease, progressive damage may continue in other organs and eventually result in death.
Treatment references
1. Gómez-Conde S, García-Castaño A, Aguirre M, et al: Molecular aspects and long-term outcome of patients with primary distal renal tubular acidosis. Pediatr Nephrol 36(10):3133-3142, 2021. doi: 10.1007/s00467-021-05066-z
2. Besouw MTP, Bienias M, Walsh P, et al: Clinical and molecular aspects of distal renal tubular acidosis in children. Pediatr Nephrol 32(6):987-996, 2017. doi: 10.1007/s00467-016-3573-4. Erratum in: Pediatr Nephrol 32(6):1095, 2017. PMID: 28188436
Key Points
Multiple defects impair proximal tubular reabsorption of glucose, phosphate, amino acids, bicarbonate, uric acid, water, potassium, and sodium.
Fanconi syndrome is usually caused by a medication or accompanies another genetic disorder.
In hereditary Fanconi syndrome, proximal tubular acidosis, hypophosphatemic rickets, hypokalemia, polyuria, and polydipsia usually appear in infancy.
Test urine for glucosuria (particularly in the presence of normal serum glucose), phosphaturia, and aminoaciduria.
Treat by giving combinations as needed of potassium or sodium with either bicarbonate or citrate, or sometimes with just a supplemental potassium salt.
