What Is Fanconi Syndrome?

Overview

Fanconi syndrome (FS) is a rare disorder that affects the filtering tubes (proximal tubules) of the kidney. 

Normally, the proximal tubules reabsorb the minerals and nutrients (metabolites) into the bloodstream that are necessary for proper functioning. In FS, the proximal tubules instead release large amounts of these essential metabolites into the urine. These essential substances include:

• water
• glucose
• phosphate
• bicarbonates
• carnitine
• potassium
• uric acid
• amino acids
• some proteins

Your kidneys filter about 180 liters (190.2 quarts) of fluids per day. More than 98 percent of this should be reabsorbed into the blood. This isn’t the case with FS. The resulting lack of essential metabolites can cause dehydration, bone deformities, and a failure to thrive.

There are treatments available that can slow or stop FS progression.

FS is most often inherited. But it also can be acquired from certain drugs, chemicals, or diseases.

It’s named after Swiss pediatrician Guido Fanconi, who described the disorder in the 1930s. Fanconi also first described a rare anemia, Fanconi anemia. This is an entirely different condition unrelated to FS.

Symptoms of Fanconi syndrome

Symptoms of inherited FS can be seen as early as infancy. They include:

• excessive thirst
• excessive urination
• vomiting
• failure to thrive
• slow growth
• frailty
• rickets
• low muscle tone
• corneal abnormalities
• kidney disease

Symptoms of acquired FS include:

• bone disease
• muscle weakness
• low blood phosphate concentration (hypophosphatemia)
• low blood potassium levels (hypokalemia)
• excess amino acids in urine (hyperaminoaciduria)

Causes of Fanconi syndrome

Inherited FS

Cystinosis is the most common cause of FS. It’s a rare inherited disease. In cystinosis, the amino acid cystine accumulates throughout the body. This leads to delayed growth and a series of disorders, such as bone deformities. The most common and severe (up to 95 percent) form of cystinosis occurs in infants and involves FS.

A 2016 review estimates 1 in every 100,000 to 200,000 newborns has cystinosis.

Other inherited metabolic diseases that can be involved with FS include:

• Lowe syndrome
• Wilson’s disease
• inherited fructose intolerance

Acquired FS

The causes of acquired FS are varied. They include:

• exposure to some chemotherapy
• use of antiretroviral drugs
• use of antibiotic drugs

Toxic side effects from therapeutic drugs are the most common cause. Usually the symptoms can be treated or reversed.

Sometimes the cause of acquired FS is unknown.

The anticancer drugs associated with FS include:

• ifosfamide
• cisplatin and carboplatin
• azacitidine
• mercaptopurine
• suramin (also used to treat parasitic diseases)

Other drugs cause FS in some people, depending on dosage and other conditions. These include:

• Expired tetracyclines. The breakdown products of expired antibiotics in the tetracycline family (anhydrotetracycline and epitetracycline) can cause FS symptoms within days.
• Aminoglycoside antibiotics. These include gentamicin, tobramycin, and amikacin. Up to 25 percent of people treated with these antibiotics develop FS symptoms, notes a 2013 review.
• Anticonvulsants. Valproic acid is one example.
• Antivirals. Theseinclude didanosine (ddI), cidofovir, and adefovir.
• Fumaric acid. This drug treatspsoriasis.
• Ranitidine. This drug treatspeptic ulcers.
• Boui-ougi-tou. This is a Chinese drug used for obesity.

Other conditions associated with FS symptoms include:

• chronic, heavy alcohol use
• glue sniffing
• exposure to heavy metals and occupational chemicals
• vitamin D deficiency
• kidney transplantation
• multiple myeloma
• amyloidosis

The exact mechanism involved with FS is not well-defined.

Diagnosis of Fanconi syndrome

Infants and children with inherited FS

Usually the symptoms of FS appear early on in infancy and childhood. Parents may notice excessive thirst or slower than normal growth. Children may have rickets or kidney problems.

Your child’s doctor will order blood and urine tests to check for abnormalities, such as high levels of glucose, phosphates, or amino acids, and to rule out other possibilities. They may also check for cystinosis by looking at the child’s cornea with a slit lamp examination. This is because cystinosis affects the eyes.

Acquired FS

Your doctor will ask for your or your child’s medical history, including any drugs you or your child is taking, other diseases present, or occupational exposures. They’ll also order blood and urine tests.

In acquired FS, you may not notice the symptoms right away. Bones and kidneys may be damaged by the time a diagnosis is made.

Acquired FS can affect people at any age.

Common misdiagnoses

Because FS is such a rare disorder, doctors may be unfamiliar with it. FS may also be present along with other rare genetic diseases, such as:

• cystinosis
• Wilson’s disease
• Dent disease
• Lowe syndrome

The symptoms may be attributed to more familiar diseases, including type 1 diabetes. Other misdiagnoses include the following:

• Stunted growth could be attributed to cystic fibrosis, chronic malnutrition, or an overactive thyroid.
• Rickets could be attributed to vitamin D deficiency or hereditary types of rickets.
• Kidney dysfunction could be attributed to a mitochondrial disorder or other rare diseases.

Treatment of Fanconi syndrome

Treatment of FS depends on its severity, cause, and the presence of other diseases. FS can’t typically be cured yet, but the symptoms can be controlled. The earlier the diagnosis and treatment, the better the outlook.

For children with inherited FS, the first line of treatment is to replace the essential substances that are being eliminated in excess by the damaged kidneys. Replacement of these substances may be by mouth or by infusion. This includes replacement of:

• electrolytes
• bicarbonates
• potassium
• vitamin D
• phosphates
• water (when the child is dehydrated)
• other minerals and nutrients

A high-calorie diet is recommended to maintain proper growth. If the child’s bones are malformed, physical therapists and orthopedic specialists may be called in.

The presence of other genetic diseases may require additional treatment. For example, a low-copper diet is recommended for people with Wilson’s disease.

In cystinosis, FS is resolved with a successful kidney transplant following renal failure. This is considered a treatment for the underlying disease, rather than a treatment for FS.