Fanconi syndrome is a complex renal disorder that may be acquired or inherited. The fundamental problem in this syndrome is the damage to the proximal renal tubule which leads to both renal and external manifestations.
A thorough history is required to determine if Fanconi syndrome is inherited. The majority of medical disorders associated with Fanconi syndrome are inherited in an autosomal recessive pattern. Hence with two heterozygous parents, the child of either gender has a ¼ chance of being homozygous for the disorder. Patients who develop Fanconi syndrome may present with the following history:
The physical findings depend on the type of Fanconi syndrome. For example some patients may have presence of cysteine crystals in the cornea which is pathognomonic for cystinosis. Other nonspecific findings include presence of hepatomegaly, which can be found in glycogenesis, galactosemia, and tyrosinemia.
The test for diagnosis of Fanconi syndrome depends on what cause is suspected . For the inherited disorder, genetic testing is done. For the acquire Fanconi syndrome, the following studies are needed:
The treatment of Fanconi syndrome irrespective of the cause involves the following :
Fanconi syndrome is also caused by accumulation of nutrients like phenylalanine, fructose, galactose and fructose because of deficiency in certain biochemical enzymes. Thus, elimination of these substances from the diet may help reverse the renal manifestation of Fanconi syndrome. Thus a dietary consult is necessary and patients should be educated about what foods they can and cannot eat. Unfortunately these disorders have other systemic manifestations like growth retardation, developmental delay, ovarian dysfunction, speech impairment or liver cirrhosis, which are not affected by restricting the diet of these substances. Individuals with Wilson disease may benefit from treatment with D-penicillamine and a low copper diet.
Over the years, several drugs have been developed that can lower levels of cysteine in the laboratory but unfortunately most have not been found to be effective clinically. The one agent that is used clinically is cysteamine bitartrate. It has been shown to lower tissue levels of cysteine, improve linear growth and delay progression of kidney disease when started early in children. However, most studies show that it does not affect progression of Fanconi syndrome.
Patients with Wilson disease are often treated with D penicillamine, which helps remove excess level of copper from the body. High doses of the drug are required for it to function well but unfortunately it does not work in all patients with Wilson disease. Patients who are not able to tolerate D-penicillamine may be treated with Trientine, but clinical experience with this agent is limited.
The prognosis of Fanconi syndrome depends on the cause and clinical presentation. The majority of patients who have inherited Fanconi syndrome have a guarded or poor prognosis .These individuals often have involvement of multiple organ systems. Those who have acquired disorder have a much improved prognosis as the primary condition can be reversed and the symptoms will improve.
Fanconi syndrome may be inherited or be acquired. In rare cases, the disorder may be idiopathic. In these patients despite exhaustive work up no identifiable cause is ever identified. In addition, individuals with idiopathic fanconi syndrome do not always present with all the features of the disorder, thus making the diagnosis difficult.
Many drugs, heavy metals and other toxins can cause Fanconi syndrome. The list includes the following:
Fanconi syndrome is either acquired or inherited. Because there are many causes of the syndrome, the exact incidence is unknown. In general, the disorder is not common but can affect people of all ages and races. Inherited cases of Fanconi syndrome are very rare but those acquired from exposure to drugs or heavy metals are slightly more common. With increased awareness of the acquired causes of Fanconi syndrome, there does appear to be a decrease in the number of reported cases.
Even though Fanconi syndrome has been shown to occur in all races, cystinosis, which is the common presentation of Fanconi syndrome in children, occurs primarily in children. The inherited Fanconi syndrome has an autosomal recessive trait and hence 25% of children will be affected.
The presentation of symptoms of Fanconi syndrome can vary. The inherited Fanconi syndrome usually presents with cystinosis and vitamin D dependent rickets within the first 12 months of life. Other inherited forms of Fanconi syndrome like Wilson disease, glycogen storage disorders, cystinosis and galactosemia may occur at a much later age. The acquired forms of cystinosis can occur at any age but usually soon after exposure to the toxic agent.
The basic defect in Fanconi syndrome is the damage to the proximal renal tubule which leads to decreased reabsorption of a number of solutes like amino acids, glucose, phosphate, bicarbonate and uric acid  . It is believed that the following causes may be the reason why solutes fail to be reabsorbed in the proximal renal tubule:
The transport of specific substances and solutes across the proximal tubule membrane is dependent on symporters and antiporters and energy is needed for these transport system to work. It is believed that defect(s) in cellular energy in the various transporters may be the overall cause of Fanconi syndrome. This may explain why so many solutes fail to get reabsorbed in the proximal renal tubules.
Fanconi syndrome that is inherited cannot be prevented. However, these patients should be seen early in childhood so that the disease can be monitored and treated as soon as possible. For patients who develop Fanconi syndrome from acquired causes, there are some preventive measures that can be undertaken. The public should be educated about limiting exposure to toxins and not take expired antibiotics like the tetracyclines or aminoglycosides. Individuals who have galactosemia should be told to avoid lactose in the diet. In addition patients with tyrosinemia should be told to avoid tyrosine and/or phenylalanine in diet to prevent the symptoms of Fanconi syndrome.
Fanconi syndrome is a disorder due to disease or defect of the proximal renal tubules of the kidney. When this segment of the renal tubules is damaged, there is failure to reabsorb amino acids, glucose, phosphate, uric acid and bicarbonate. The disorder may be inherited or acquired after exposure to certain drugs, toxins or heavy metals. There are many other causes of Fanconi syndrome and the manifestations depend on the cause. When there is continual loss of bicarbonate, patients often develop renal tubular acidosis. When there is loss of phosphate, bone disease develops as this mineral is essential for normal skeletal growth. It is vital not to confuse Fanconi syndrome with Fanconi anemia, which is a completely distinct and separate disorder   .
Patients should be informed that Fanconi syndrome may be inherited or acquired. There are many cases of acquired Fanconi syndrome, ranging from drugs, toxins and other metabolic disorders. The predominant feature of the disease is renal defects which can lead to renal failure. The acquired form of Fanconi syndrome can be treated if the offending agent is withdrawn but the inherited forms of Fanconi syndrome usually have a poor prognosis. All patients with Fanconi syndrome need close follow up with a specialist to ensure that the disease is not progressing. A dietary consult may help some patients with Fanconi syndrome. Parents with children affected by inherited Fanconi syndrome should receive genetic counseling so that they can understand the pattern of inheritance. This may help if they want to have additional children in future.