Fanconi syndrome or Fanconi's syndrome (, ) is a

syndrome A syndrome is a set of medical signs and symptoms which are correlated with each other and often associated with a particular disease or disorder. The word derives from the Greek language, Greek σύνδρομον, meaning "concurrence". When a sy ...

of inadequate

reabsorption In renal physiology, reabsorption, more specifically tubular reabsorption, is the process by which the nephron removes water and solutes from the tubular fluid (pre-urine) and returns them to the circulating blood. It is called ''reabsorption' ...

in the proximal renal tubules of the

kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...

. The syndrome can be caused by various underlying congenital or acquired

disease A disease is a particular abnormal condition that adversely affects the structure or function (biology), function of all or part of an organism and is not immediately due to any external injury. Diseases are often known to be medical condi ...

s, by

toxicity Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacteria, bacterium, or plant, as well as the effect o ...

(for example, from toxic heavy metals), or by adverse drug reactions. It results in various small molecules of

metabolism Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

being passed into the

urine Urine is a liquid by-product of metabolism in humans and many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...

instead of being reabsorbed from the tubular fluid (for example,

glucose Glucose is a sugar with the Chemical formula#Molecular formula, molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae d ...

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

uric acid Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the Chemical formula, formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the meta ...

phosphate Phosphates are the naturally occurring form of the element phosphorus. In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthop ...

, and

bicarbonate In inorganic chemistry, bicarbonate (IUPAC-recommended nomenclature: hydrogencarbonate) is an intermediate form in the deprotonation of carbonic acid. It is a polyatomic anion with the chemical formula . Bicarbonate serves a crucial bioche ...

). Fanconi syndrome affects the proximal tubules, namely, the proximal convoluted tubule (PCT), which is the first part of the tubule to process fluid after it is filtered through the glomerulus, and the proximal straight tubule (pars recta), which leads to the descending limb of loop of Henle. 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 diseases

rickets Rickets, scientific nomenclature: rachitis (from Greek , meaning 'in or of the spine'), is a condition that results in weak or soft bones in children and may have either dietary deficiency or genetic causes. Symptoms include bowed legs, stun ...

and

osteomalacia Osteomalacia is a disease characterized by the softening of the bones caused by impaired bone metabolism primarily due to inadequate levels of available phosphate, calcium, and vitamin D, or because of resorption of calcium. The impairment of b ...

(even with adequate

vitamin D Vitamin D is a group of structurally related, fat-soluble compounds responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, along with numerous other biological functions. In humans, the most important compo ...

and

calcium Calcium is a chemical element; it has symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to it ...

levels), because phosphate is necessary for bone development in children and even for ongoing bone metabolism in adults.

Presentation

The clinical features of proximal renal tubular acidosis are: *

Polyuria Polyuria () is excessive or an abnormally large production or Frequent urination, passage of urine (greater than 2.5 L or 3 L over 24 hours in adults). Increased production and passage of urine may also be termed as diuresis. Polyuria often appe ...

, polydipsia and

dehydration In physiology, dehydration is a lack of total body water that disrupts metabolic processes. It occurs when free water loss exceeds intake, often resulting from excessive sweating, health conditions, or inadequate consumption of water. Mild deh ...

* Hypophosphatemic

(in children) and

(in adults) * Growth failure * Acidosis * Hypokalemia * Hyperchloremia Other features of the generalized proximal tubular dysfunction of the Fanconi syndrome are: *

Hypophosphatemia Hypophosphatemia is an electrolyte disorder in which there is a low level of phosphate in the blood. Symptoms may include weakness, trouble breathing, and loss of appetite. Complications may include seizures, coma, rhabdomyolysis, or soft ...

/ hyperphosphaturia * Glycosuria * Proteinuria/aminoaciduria * Hyperuricosuria

Causes

In contrast to

Hartnup disease Hartnup disease (also known as " pellagra-like dermatosis" and "Hartnup disorder") is an autosomal recessive metabolic disorder affecting the absorption of nonpolar amino acids (particularly tryptophan that can be, in turn, converted into se ...

and related tubular conditions, Fanconi syndrome affects the transport of many different substances, so is not considered to be a defect in a specific channel, but a more general defect in the function of the proximal tubules. Different diseases underlie Fanconi syndrome; they can be inherited,

congenital A birth defect is an abnormal condition that is present at childbirth, birth, regardless of its cause. Birth defects may result in disability, disabilities that may be physical disability, physical, intellectual disability, intellectual, or dev ...

, or acquired.

Inherited

Cystinosis is the most common cause of Fanconi syndrome in children. Other recognised causes are Wilson's disease (a genetically inherited condition of copper metabolism), Lowe syndrome, tyrosinemia (type I),

galactosemia Galactosemia (British galactosaemia, from Greek γαλακτόζη + αίμα, meaning galactose + blood, accumulation of galactose in blood) is a rare genetics, genetic Metabolism, metabolic Disease, disorder that affects an individual's ability t ...

, glycogen storage diseases, and hereditary fructose intolerance. Two forms, Dent's disease and Lowe syndrome, are X linked. A recently described form of this disease is due to a mutation in the peroxisomal protein EHHADH. This mutation misdirects the EHHADH to the mitochondria. This interferes with respiratory complex I and with beta oxidation of fatty acids. The result is a decrease in the ability of the mitochondria to produce ATP. It was shown that a specific mutation (R76W) of '' HNF4A'', a gene encoding a transcription factor, causes Fanconi syndrome in human. In the kidney, ''HNF4A'' is expressed in the proximal tubules specifically. Deletion of ''Hnf4a'' in the developing mouse kidney caused Fanconi syndrome phenotypes including polyruia, polydipsia, glycosuria, and phosphaturia. The ''Hnf4a'' mutant kidney showed a defect in the formation of proximal tubules.

Acquired

It is possible to acquire this disease later in life. Causes include ingesting expired tetracyclines (where tetracycline changes to form epitetracycline and anhydrotetracycline which damage the proximal tubule), and as a side effect of

tenofovir Tenofovir disoproxil, sold under the brand name Viread among others, is a medication used to treat chronic hepatitis B and to prevent and treat HIV/AIDS. It is generally recommended for use with other antiretrovirals. It may be used for pr ...

in cases of pre-existing renal impairment. In the HIV population, Fanconi syndrome can develop secondary to the use of an antiretroviral regimen containing

and didanosine.

Lead poisoning Lead poisoning, also known as plumbism and saturnism, is a type of metal poisoning caused by lead in the body. Symptoms may include abdominal pain, constipation, headaches, irritability, memory problems, infertility, numbness and paresthesia, t ...

also leads to Fanconi syndrome.

Multiple myeloma Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibody, antibodies. Often, no symptoms are noticed initially. As it progresses, bone ...

or monoclonal gammopathy of undetermined significance can also cause the condition. Additionally, Fanconi syndrome can develop as a secondary or tertiary effect of certain autoimmune disorders.

Diagnosis

Fanconi syndrome is diagnosed through a combination of physical examination, blood and urine tests, and potentially genetic testing. Key findings include high levels of glucose, amino acids, and phosphate in the urine despite normal or low blood levels of these substances, and low levels of phosphate, bicarbonate, and potassium in the blood.

Treatment

Treatment of children with Fanconi syndrome mainly consists of replacement of substances lost in the

(mainly fluid and bicarbonate).

Eponym

It is named after Guido Fanconi, a Swiss pediatrician, although various other scientists, including George Lignac, contributed to its study. It should not be confused with Fanconi anemia, a separate disease.

References

External links

{{Nephrology Amino acid metabolism disorders Kidney diseases Syndromes