What Is Fanconi Syndrome?

Overview

Fanconi Syndrome is a rare disorder where the kidneys cannot carry out their function of filtering blood and reabsorbing electrolytes and useful substances, leading to their excretion in the urine.

The condition is either inherited or acquired and may be caused by genetic mutations, exposure to toxins, or certain medications. The inherited form of Fanconi Syndrome  (also known as primary Fanconi Syndrome) is quite common among children. The acquired form of Fanconi Syndrome (also known as secondary Fanconi Syndrome) is more common among adults, and can be acquired after exposure to chemotherapy, heavy metals etc or as a side effect of vitamin D deficiency, kidney transplantation, and multiple myeloma.¹

The symptoms of Fanconi Syndrome include the excretion of large amounts of urine with traces of electrolytes, dehydration, electrolyte imbalances, bone problems, and growth delays in children.

Fanconi Syndrome is due to a defect in the first segment of the nephron. Nephrons are the kidney’s filtering units. Electrolytes are reabsorbed in the section of the nephron, which is called the proximal tubule. Defects in the proximal tubule leave it unable to reabsorb electrolytes,

such as glucose, bicarbonate, phosphorus, uric acid, and certain amino acids, causing them to be excreted in urine.¹

This article explores the causes of Fanconi Syndrome, the signs and symptoms to look out for, how it is diagnosed, and how best to manage it. We encourage you to keep reading if you want to know more about any of these areas.

Causes of fanconi syndrome 

Inherited (or primary) Fanconi Syndrome is most commonly seen in children and is caused by genetic mutations. These mutations damage the kidney (either directly or indirectly) and leave it unable to filter your blood correctly. These defects include: 

• Cystinosis: This refers to the accumulation of the amino acid cystine within cells. Cystinosis is the most common cause of Fanconi Syndrome and can affect the eyes, kidneys, brain, muscles, liver, thyroid, pancreas, and testes.
• Fructose intolerance: The inability to break down fructose (a type of sugar found in fruit) due to a lack of the enzyme required for this process. This can be passed down among families.
• Galactosemia: Accumulation of galactose (sugar) in the blood to toxic levels due to the inability of the body to use it
• Glycogen storage disease: Where the body lacks the enzyme needed to break down glycogen (stored glucose) for energy, causing it to accumulate in the liver and muscles
• Lowe syndrome: Lowe syndrome affects the eyes, nervous system, and kidneys. It is caused by mutations in the OCRL gene, which encodes an enzyme needed to produce cell membranes.
• Dent disease: Causes the kidney’s nephrons and proximal tubule to become dysfunctional. Dent disease is characterised by increased levels of protein and calcium in the urine 
• Wilson disease: This occurs when the body accumulates too much copper in the liver, brain, eyes, and other organs

Unlike inherited Fanconi Syndrome, the acquired form of the disease (which is more common in adults) has various known causes, including:

• Exposure to heavy metals: The kidney is one of several organs that can be damaged by heavy metals. Heavy metals, such as lead, are found in the environment and are very harmful to our health. Heavy metals can stop the kidney from reabsorbing electrolytes and trigger the accumulation of harmful metals within the kidney and the rest of the body.² 
• Kidney transplantation: Immunosuppressive medications given to kidney transplant patients, damage to transplanted organs, or organ rejection can all trigger Fanconi Syndrome
• Multiple myeloma: Multiple myeloma is a type of blood cancer that forms in a type of white blood cells known as “plasma cells”. Cancerous plasma cells may produce abnormal proteins, which can trigger Fanconi Syndrome.  
• Drugs: Certain chemotherapy and antiretroviral drugs like cisplatin, Ifosfamide, tenofovir, valproic acid, gentamicin, and deferasirox can have toxic side effects on the kidney
• Amyloidosis: A rare and incurable condition where amyloid proteins build up in the body’s organs, including the kidney 

Research has it that honeybee stings can also cause Fanconi syndrome.³

Signs and symptoms of fanconi syndrome 

The symptoms of Fanconi Syndrome can begin at any age. 

Some of the known signs and symptoms of inherited Fanconi Syndrome include:

• Slow growth 
• Chronic kidney disease
• Dehydration
• Frequent urination 
• Weakening of bone and muscles
• Fracture of bones
• Osteomalacia (shortening of the bones)

In adults, the symptoms do not develop until the condition has been present for some time. Some of the known signs and symptoms of acquired Fanconi Syndrome include:

• Bone weakness and pain
• Hypophosphatemia (Low phosphate levels in blood)
• Metabolic acidosis (Acid buildup in body fluids)
• Hyperaminoaciduria (High levels of amino acids present in the urine)
• Polydipsia (Excessive thirst)
• Peeing more than usual
• Dehydration

Diagnosis of fanconi syndrome 

To confirm the presence of Fanconi syndrome, tests are carried out using your urine or blood samples.

For the urine test (also referred to as urinalysis), your doctor will collect a sample of your urine and send it to a laboratory for analysis. The presence of high levels of glucose, amino acids, and phosphates in your urine indicates Fanconi syndrome.

In the case of blood tests, a needle is used to draw a small amount of blood from a vein in your arm. Like urine, this blood will also be sent to the laboratory for analysis. A low level of phosphate, bicarbonate, and potassium in the blood indicates the signs of Fanconi syndrome.

You may experience some discomfort, bruising, soreness, or light bleeding after the collection of the blood. These are all completely normal and usually go away within a day or two.

Management and treatment of fanconi syndrome 

Most cases of inherited Fanconi Syndrome can not be cured and for acquired cases there is potential to recover, however, there isn’t a guarantee. Doctors can help you manage the symptoms you experience. This will depend on the underlying cause and severity of your illness, and whether you have any other illnesses. 

The primary therapy for Fanconi Syndrome is to treat the underlying causes of the disease and to replace the electrolytes and other substances lost in the urine. These electrolytes can be administered orally or through an IV infusion (intravenous).

Due to Fanconi Syndrome’s impact on normal growth, high-calorie and nutrient-rich diets are often recommended to patients. In more severe cases where the bones are malformed, patients may need to undergo physical therapy or orthopaedic procedures.

As mentioned above, acquired Fanconi Syndrome is often associated with other diseases, which need to be treated to restore normal kidney function. For example, if Fanconi Syndrome is due to hypophosphatemia then your healthcare provider might prescribe a phosphate supplement along with vitamin D, if it is due to metabolic acidosis your healthcare provider will prescribe sodium bicarbonate to help restore a healthy blood pH balance.¹

FAQs

How can I prevent fanconi syndrome? 

Inherited cases of  Fanconi Syndrome cannot be prevented. However, genetic testing can help diagnose Fanconi Syndrome early and in time to establish proper management strategies.

 Acquired Fanconi syndrome can be prevented by:

• Avoiding exposure to lead and other heavy metals
• Discussing herbal supplements with a healthcare provider before using them
• Check with your healthcare provider about the usage of chemotherapy drugs or medications

How common is Fanconi Syndrome? 

Fanconi Syndrome is a rare disease of the kidney. 

Who is at risk of Fanconi Syndrome? 

• Children whose parents have Fanconi Syndrome 
• Those who are frequently exposed to lead or other toxic substances 
• Those using antiretroviral drugs or undergoing chemotherapy

When should I see a doctor? 

At the sight or notice of any symptoms of Fanconi Syndrome, you should see a doctor for proper diagnosis and appropriate treatment.

Summary 

Fanconi Syndrome is a rare disease that affects the proximal tubule of the kidney. Its role is to help the kidney reabsorb electrolytes. Fanconi Syndrome is characterized by the presence of electrolytes, glucose, bicarbonates, phosphates, uric acid, potassium, and amino acids in the urine and can be primary (inherited) or secondary (acquired). The primary form is quite common among children and is largely caused by genetic mutations. The secondary form is more common in adults and is associated with heavy metal exposure and the use of chemotherapeutic or antiretroviral drugs. The secondary form of Fanconi Syndrome is also associated with diseases such as cystinosis, Lowe syndrome, Dent Disease, etc. 

The symptoms associated with Fanconi Syndrome include weakness of the muscle, fatigue, osteomalacia, frequent urination, and slow growth. Fanconi Syndrome is usually diagnosed by carrying out tests on the patient's blood and urine samples, and once diagnosed, it can be managed by treating underlying diseases and replacing lost electrolytes orally and/or parenterally. If you notice any symptoms of Fanconi Syndrome, you should see a doctor for proper diagnosis and appropriate treatment.