Fanconi syndrome
Encyclopedia
Falconi syndrome is a disease of the proximal renal tubules of the kidney
in which glucose
, amino acid
s, uric acid
, phosphate
and bicarbonate
are passed into the urine, instead of being reabsorbed. Fanconi syndrome affects the proximal tubule, which is the first part of the tubule to process fluid after it is filtered through the glomerulus. It may be inherited, or caused by drugs or heavy metals.
Different forms of Fanconi syndrome can affect different functions of the proximal tubule, and result in different complications. The loss of bicarbonate
results in Type 2 or proximal renal tubular acidosis
. The loss of phosphate results in the bone disease rickets
(even with adequate vitamin D and calcium), because phosphate is necessary for bone development.
, a Swiss pediatrician; this may be a misnomer since Fanconi himself never identified it as a syndrome; though, as in the case of Goodpasture's syndrome
, it is customary to name a syndrome after the first person to note a constellation of symptoms as occurring together.
It should not be confused with Fanconi anemia
, a separate disease.
Other features of the generalized proximal tubular dysfunction of the Fanconi syndrome are:
and related tubular conditions, Fanconi syndrome affects the transport of many different substances, and therefore is not considered to be a defect in a specific channel, but a more general defect in the function of the proximal tubules.
There are different diseases underlying Fanconi syndrome. They can be inherited
, congenital or acquired.
is the most common cause of Fanconi syndrome in children.
Other recognised causes of Fanconi's syndrome are Wilson's disease
(a genetically inherited condition of copper metabolism), Lowe syndrome, tyrosinemia
(Type I), galactosemia
, glycogen storage diseases, and fructose intolerance
.
Two forms, Dent's disease
and Lowe syndrome, are X linked.
Causes include ingesting expired tetracyclines, and as a side effect of tenofovir in cases of preexisting renal impairment. In the HIV population, Fanconi syndrome can develop secondary to use of an antiretroviral regimen containing tenofovir and didanosine
.
Lead poisoning
also leads to Fanconi syndrome.
Monoclonal gammopathy of undetermined significance
can also cause the condition.
Multiple myeloma
is also a known cause.
(mainly fluid and bicarbonate).
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
in which glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
, amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s, uric acid
Uric acid
Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates such as ammonium acid urate. Uric acid is created when the body breaks down purine nucleotides. High blood concentrations of uric acid...
, phosphate
Phosphate
A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...
and bicarbonate
Bicarbonate
In inorganic chemistry, bicarbonate is an intermediate form in the deprotonation of carbonic acid...
are passed into the urine, instead of being reabsorbed. Fanconi syndrome affects the proximal tubule, which is the first part of the tubule to process fluid after it is filtered through the glomerulus. It may be inherited, or caused by drugs or heavy metals.
Different forms of Fanconi syndrome can affect different functions of the proximal tubule, and result in different complications. The loss of bicarbonate
Bicarbonate
In inorganic chemistry, bicarbonate is an intermediate form in the deprotonation of carbonic acid...
results in Type 2 or proximal renal tubular acidosis
Renal tubular acidosis
Renal tubular acidosis is a medical condition that involves an accumulation of acid in the body due to a failure of the kidneys to appropriately acidify the urine. When blood is filtered by the kidney, the filtrate passes through the tubules of the nephron, allowing for exchange of salts, acid...
. The loss of phosphate results in the bone disease rickets
Rickets
Rickets is a softening of bones in children due to deficiency or impaired metabolism of vitamin D, magnesium , phosphorus or calcium, potentially leading to fractures and deformity. Rickets is among the most frequent childhood diseases in many developing countries...
(even with adequate vitamin D and calcium), because phosphate is necessary for bone development.
Eponym
It is named after Guido FanconiGuido Fanconi
Guido Fanconi was a Swiss pediatrician. He was born in Poschiavo, Canton Grisons in the Italian-speaking region of Switzerland. Fanconi is regarded as one of the founders of modern pediatrics....
, a Swiss pediatrician; this may be a misnomer since Fanconi himself never identified it as a syndrome; though, as in the case of Goodpasture's syndrome
Goodpasture's syndrome
Goodpasture’s syndrome is a rare disease characterized by glomerulonephritis and hemorrhaging of the lungs...
, it is customary to name a syndrome after the first person to note a constellation of symptoms as occurring together.
It should not be confused with Fanconi anemia
Fanconi anemia
Fanconi anemia is a genetic disease with an incidence of 1 per 350,000 births, with a higher frequency in Ashkenazi Jews and Afrikaners in South Africa.FA is the result of a genetic defect in a cluster of proteins responsible for DNA repair...
, a separate disease.
Clinical features
The clinical features of proximal renal tubular acidosis are:- PolyuriaPolyuriaPolyuria is a condition usually defined as excessive or abnormally large production or passage of urine . Frequent urination is sometimes included by definition, but is nonetheless usually an accompanying symptom...
, polydipsiaPolydipsiaPolydipsia is a medical symptom in which the patient displays excessive thirst. The word derives from the Greek πολυδιψία, which is derived from πολύς + δίψα...
and dehydrationDehydrationIn physiology and medicine, dehydration is defined as the excessive loss of body fluid. It is literally the removal of water from an object; however, in physiological terms, it entails a deficiency of fluid within an organism... - Hypophosphatemic ricketsRicketsRickets is a softening of bones in children due to deficiency or impaired metabolism of vitamin D, magnesium , phosphorus or calcium, potentially leading to fractures and deformity. Rickets is among the most frequent childhood diseases in many developing countries...
(in children) and osteomalaciaOsteomalaciaOsteomalacia is the softening of the bones caused by defective bone mineralization secondary to inadequate amounts of available phosphorus and calcium, or because of overactive resorption of calcium from the bone as a result of hyperparathyroidism...
(in adults) - Growth failure
- AcidosisAcidosisAcidosis is an increased acidity in the blood and other body tissue . If not further qualified, it usually refers to acidity of the blood plasma....
- HypokalemiaHypokalemiaHypokalemia or hypokalaemia , also hypopotassemia or hypopotassaemia , refers to the condition in which the concentration of potassium in the blood is low...
- HyperchloremiaHyperchloremiaHyperchloremia is an electrolyte disturbance in which there is an abnormally elevated level of the chloride ion in the blood. The normal serum range for chloride is 97 to 107 mEq/L. Hyperchloremia is defined as a chloride concentration exceeding this level....
Other features of the generalized proximal tubular dysfunction of the Fanconi syndrome are:
- HypophosphatemiaHypophosphatemiaHypophosphatemia is an electrolyte disturbance in which there is an abnormally low level of phosphate in the blood. The condition has many causes, but is most commonly seen when malnourished patients are given large amounts of carbohydrates, which creates a high phosphorus demand by cells,...
/phosphaturia - GlycosuriaGlycosuriaGlycosuria or glucosuria is the excretion of glucose into the urine. Ordinarily, urine contains no glucose because the kidneys are able to reclaim all of the filtered glucose back into the bloodstream. Glycosuria is nearly always caused by elevated blood glucose levels, most commonly due to...
- ProteinuriaProteinuriaProteinuria means the presence of anexcess of serum proteins in the urine. The protein in the urine often causes the urine to become foamy, although foamy urine may also be caused by bilirubin in the urine , retrograde ejaculation, pneumaturia due to a fistula, or drugs such as pyridium.- Causes...
/aminoaciduria - HyperuricosuriaHyperuricosuriaHyperuricosuria is a medical term referring to the presence of excessive amounts of uric acid in the urine. Notable direct causes of hyperuricosuria are dissolution of uric acid crystals in the kidneys or urinary bladder, and hyperuricemia...
Causes
In contrast to Hartnup diseaseHartnup disease
Hartnup disease is an autosomal recessive metabolic disorder affecting the absorption of nonpolar amino acids...
and related tubular conditions, Fanconi syndrome affects the transport of many different substances, and therefore is not considered to be a defect in a specific channel, but a more general defect in the function of the proximal tubules.
There are different diseases underlying Fanconi syndrome. They can be inherited
Inheritance
Inheritance is the practice of passing on property, titles, debts, rights and obligations upon the death of an individual. It has long played an important role in human societies...
, congenital or acquired.
Inherited
CystinosisCystinosis
Cystinosis is a lysosomal storage disease characterized by the abnormal accumulation of the amino acid cystine. It is a genetic disorder that typically follows an autosomal recessive inheritance pattern. Cystinosis is the most common cause of Fanconi syndrome in the pediatric age group...
is the most common cause of Fanconi syndrome in children.
Other recognised causes of Fanconi's syndrome are Wilson's disease
Wilson's disease
Wilson's disease or hepatolenticular degeneration is an autosomal recessive genetic disorder in which copper accumulates in tissues; this manifests as neurological or psychiatric symptoms and liver disease...
(a genetically inherited condition of copper metabolism), Lowe syndrome, tyrosinemia
Tyrosinemia
Tyrosinemia is an error of metabolism, usually inborn, in which the body cannot effectively break down the amino acid tyrosine. Symptoms include liver and kidney disturbances and mental retardation...
(Type I), galactosemia
Galactosemia
Galactosemia is a rare genetic metabolic disorder that affects an individual's ability to metabolize the sugar galactose properly. Although the sugar lactose can metabolize to galactose, galactosemia is not related to and should not be confused with lactose intolerance...
, glycogen storage diseases, and fructose intolerance
Fructose intolerance
Hereditary fructose intolerance or fructose poisoning is a hereditary condition caused by a deficiency of liver enzymes that metabolise fructose...
.
Two forms, Dent's disease
Dent's disease
Dent's disease is a rare X-linked recessive inherited condition that affects the proximal renal tubules of the kidney. It is one cause of Fanconi syndrome, and is characterized by tubular proteinuria, hypercalciuria, calcium nephrolithiasis, nephrocalcinosis and chronic renal failure."Dent's...
and Lowe syndrome, are X linked.
Acquired
It is possible to acquire this disease later in life.Causes include ingesting expired tetracyclines, and as a side effect of tenofovir in cases of preexisting renal impairment. In the HIV population, Fanconi syndrome can develop secondary to use of an antiretroviral regimen containing tenofovir and didanosine
Didanosine
Didanosine is sold under the trade names Videx and Videx EC. It is a reverse transcriptase inhibitor, effective against HIV and used in combination with other antiretroviral drug therapy as part of highly active antiretroviral therapy .-History:The related pro-drug of didanosine,...
.
Lead poisoning
Lead poisoning
Lead poisoning is a medical condition caused by increased levels of the heavy metal lead in the body. Lead interferes with a variety of body processes and is toxic to many organs and tissues including the heart, bones, intestines, kidneys, and reproductive and nervous systems...
also leads to Fanconi syndrome.
Monoclonal gammopathy of undetermined significance
Monoclonal gammopathy of undetermined significance
Monoclonal gammopathy of undetermined significance , formerly benign monoclonal gammopathy, is a condition in which a paraprotein is found in the blood during standard laboratory tests...
can also cause the condition.
Multiple myeloma
Multiple myeloma
Multiple myeloma , also known as plasma cell myeloma or Kahler's disease , is a cancer of plasma cells, a type of white blood cell normally responsible for the production of antibodies...
is also a known cause.
Treatment
Treatment of children with Fanconi syndrome mainly consists of replacement of substances lost in the urineUrine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
(mainly fluid and bicarbonate).