What is Fanconi Syndrome?
Fanconi syndrome is a condition where the kidneys’ tubes, specifically the ‘proximal tubule’, don’t properly absorb various substances and minerals that they usually should. This problem can either be passed down from parents to children (inherited) or develop later in life (acquired). Also, it’s important to avoid confusing it with Fanconi anemia. This is a different, rare condition that often includes fewer red and white blood cells and platelets than normal, underdeveloped bone marrow, irregular skin color due to extra melanin, and various birth defects.
For people diagnosed with Fanconi syndrome, adults typically have the acquired type, while children usually have the inherited type. The possibility of treating this condition depends on what exactly caused it. Generally, the approach is to treat the root cause (if there is one), and balance any issues with hydration (volume), nutrients (nutrition), or mineral levels (electrolytes). The definition of “Fanconi syndrome” suggests that the entire tubule in the kidney isn’t working correctly.
In people with this syndrome, the substances that the kidney tubule usually absorbs don’t get absorbed as they should.
What Causes Fanconi Syndrome?
Fanconi syndrome can be caused by several genetic conditions, including: cystinosis, galactosemia (a rare genetic metabolic disorder), hereditary fructose intolerance, tyrosinemia, Wilson disease, Lowe syndrome, Dent disease, glycogenosis, mitochondrial cytopathies, and some unknown conditions.
Aside from these inherited causes, Fanconi syndrome can also be acquired. This happens due to certain medications like antivirals (specifically, nucleoside reverse transcriptase inhibitors), chemotherapy drugs (such as cisplatin), immune system suppressing drugs (like azathioprine), antibiotics (gentamicin), and various other medicines.
Other factors that could lead to Fanconi syndrome are medical conditions like monoclonal gammopathy (an abnormal protein in the blood), lead poisoning, and exposure to other harmful substances. In some cases, more general kidney issues can also result in Fanconi syndrome. These include complications after kidney transplant, specific causes of nephrotic syndrome (a kidney disorder causing your body to excrete too much protein in your urine), and acute tubular necrosis (a kidney disease caused due to lack of blood and oxygen).
It’s interesting to note that honeybee stings and Legionella pneumonia (a type of pneumonia caused by Legionella bacteria) can result in Fanconi syndrome, but the exact reason for this is not yet understood.
Risk Factors and Frequency for Fanconi Syndrome
Fanconi syndrome is a complex condition influenced by a mix of factors which can be genetic or come from outside the body, making it hard to measure how often it occurs. If a person inherits the condition, it’s usually found more often in young, white children. This is because a common form of Fanconi syndrome, known as cystinosis, mostly happens in white people.
Signs and Symptoms of Fanconi Syndrome
When a patient is suspected to have Fanconi syndrome, it’s important to determine whether it’s inherited or acquired. The healthcare provider should ask if the patient has any symptoms or a diagnosed medical condition such as cystinosis, Wilson disease, hereditary fructose intolerance, or Lowe syndrome. The doctor should also check if the patient has a history of multiple myeloma or kidney transplant, or if they have used certain medications including valproic acid, ddI, cidofovir, adefovir, tenofovir, ifosfamide, lenalidomide, streptozocin, or ranitidine. Specifically, leukemia is another illness that has been associated with this condition.
During a physical examination, the doctor may discover that the patient is discharging an unusually high amount of substances such as amino acids, calcium, bicarbonate, glucose, phosphate, and uric acid in their urine. Signs associated with the loss of these substances may include dehydration, abnormal balance of minerals in the body, rickets, osteomalacia, and growth failure. Specific symptoms of osteomalacia are unexplained bone fractures and widespread bone pain in the hip area. Besides, children may show signs of rickets, a condition characterized by bone deformities.
This illness can also cause individuals to lose excessive amounts of water and minerals, leading to symptoms such as thirst, fatigue, muscle weakness, and frequent urination. A decrease in phosphate levels could lead to neuro-muscular issues like numbness, shakiness, and muscle weakness. In severe cases, this could affect heart muscle function and pose difficulties in weaning patients off mechanical ventilation. In some rare cases, extreme muscular damage can occur due to severe phosphate reduction.
If Fanconi syndrome is associated with cystinosis, the patient may present with deposits of the amino acid cystine in their bone marrow, liver, cornea (visible as crystals) and kidneys. The patient may have a history of cystine stone formation, which may sometimes result in significant kidney stones in advanced stages. In cases unrelated to cystinosis, the release of amino acids in urine due to Fanconi syndrome is generally insignificant and doesn’t cause a metabolic issue.
Testing for Fanconi Syndrome
If your doctor suspects that you might have a condition called Fanconi syndrome, they might ask you to take several tests. These tests would look at different components in your blood and urine to help the doctor understand what’s happening in your body.
Some urine tests are used to examine certain substances in the body known as uric acid, glucose, beta2-microglobulin and N-acetyl-beta-D-glucosaminidase. If these are found in higher than usual levels, it might suggest Fanconi syndrome.
Blood tests may be used to check for lower levels of potassium and phosphate, and higher levels of chloride. All these factors can also indicate the syndrome. Also, your doctor might look at how much amino acid, phosphate, bicarbonate, and glucose your body gets rid of in a 24-hour period through urine. If these levels are higher than normal, it can also be another clue about the diagnosis.
Some more specialized tests might involve checking your levels of a substance called urinary retinol binding protein 4 and comparing how much lactate and creatinine you have in your urine. These might also help your doctor confirm the diagnosis.
Finally, your doctor might want to rule out other disorders—like cystinosis, which could also cause similar symptoms. This can be done by measuring specific enzyme levels. They might also check for any evidence of drugs or heavy metals in your blood or urine, as these can sometimes cause Fanconi syndrome.
Treatment Options for Fanconi Syndrome
In general, it’s crucial to avoid becoming dehydrated and to make up for any vital minerals such as potassium, phosphate, and bicarbonate that your body has lost if you have Fanconi syndrome. Doctors generally don’t see the need to replace amino acids, and the effectiveness of a substance called carnitine for this condition is still unclear.
Fanconi syndrome is best treated by addressing the underlying cause, but because there could be many different causes, there isn’t a straightforward or uniform treatment approach. Making sure your body has enough bicarbonate and potassium is an important part of management, but these measures aren’t enough to completely resolve the condition in the long term.
If the syndrome is caused by a specific medication or suspicion of heavy metal poisoning, it’s strongly advised to avoid or remove the harmful substance causing the condition.
What else can Fanconi Syndrome be?
Drinking and urinating excessively, often observed in Fanconi syndrome, can be caused by two conditions known as diabetes mellitus and diabetes insipidus. Additionally, lack of Vitamin D or calcium can lead to conditions called rickets or osteomalacia, which affect the bones.
Recovery from Fanconi Syndrome
After being diagnosed, it’s crucial for patients to be observed regularly. Aspects to watch out for include the amount of urine they’re producing, their electrolyte levels, and the levels of medication they’re taking.
