Fanconi syndrome: what is it, symptoms, treatment, prognosis

What is Fanconi Syndrome?

Fanconi syndrome - This is a defect in the proximal renal tubule, leading to malabsorption of various electrolytes and substances that are usually absorbed by the proximal tubule. The condition can be hereditary or acquired. This disease should not be confused with Fanconi anemic, which is a rare recessive disease characterized by pancytopenia, hypoplasia of the bone marrow, spotty brown discoloration of integuments due to deposition of melanin and associated with multiple congenital anomalies. Adults with Fanconi syndrome are usually of the acquired type and children with the syndrome are of the genetic type. The ability to treat a condition depends on its specific etiology and usually involves correcting root cause, if any, and correction of volumetric, nutritional, or electrolytic deficit. The definition of "Fanconi syndrome" implies a global defect in the tubule. Any solutes normally reabsorbed by the tubule are not adequately reabsorbed in a patient with this syndrome.

Signs and symptoms

Symptoms of a hereditary disease can be seen as early as infancy. They include:

• excessive thirst;
• excessive urination;
• vomiting;
• growth disorder;
• fragility of bones;
• rickets;
• low muscle tone;
• corneal abnormalities;
• kidney disease.

Acquired disease symptoms include:

• bone disease;
• muscle weakness;
• low concentration of phosphates in the blood (hypophosphatemia);
• low blood potassium (hypokalemia);;
• excess amino acids in the urine (hyperaminoaciduria).

Causes and risk factors

There are at least 10 hereditary causes of Fanconi syndrome, including:

• cystinosis;
• galactosemia;
• hereditary fructose intolerance;
• tyrosinemia;
• Wilson-Konovalov disease;
• Lowe's syndrome;
• Dent's disease;
• glycogenosis;
• mitochondrial cytopathies;
• idiopathic diseases.

There are also several acquired causes, including:

• Taking certain antiviral drugs (nucleoside reverse transcriptase inhibitors [NRTIs]);
• chemotherapeutic agents (cisplatin);
• immunosuppressants (azathioprine);
• antibiotics (gentamicin) or certain other medicines.

In addition, the condition may be associated with monoclonal gammopathy, lead poisoning and other toxins. More common kidney damage, such as secondary to kidney transplantation, specific causes of nephrotic syndrome, and acute tubular necrosis. Honey bee stings can also cause Fanconi syndrome. Legionella pneumonia (legionnaires disease) can also cause Fanconi syndrome for unknown reasons.

Epidemiology

It is difficult to assess the epidemiology of Fanconi syndrome as it encompasses a wide range of acquired, inherited, and exogenous factors that are unrelated to each other. If the disease is inherited, then it is more often observed in young Caucasians, since cystinosis occurs almost exclusively in Caucasians and is a common form of the syndrome Fanconi.

Pathophysiology

Several mechanisms can cause Fanconi syndrome, some of which may not be fully understood. These mechanisms include a decrease in the flow of solute into the blood from the tubular epithelium, an increase in the backflow of solute through the tight junctions that separate cells, lining the tubular epithelium, from blood to glomerular filtrate, impaired flow of solute into the epithelium of the tubules and leakage of solute back into the lumen from the tubular epithelium. This could be due to a more serious problem with generating the energy needed by cells to complete a task. for the delivery of solutes through the brush border membrane or for the transport of solutes through the basolateral membrane. For example, heavy metal poisoning can compromise mitochondrial energy use.

Fanconi's syndrome requires that the distal nephron does not absorb solutes, which are reabsorbed primarily by the proximal convoluted tubule. Impaired absorption of these substances can be associated with a change in the permeability of the tubular membranes or problems with transport vehicles. Substances that they do not absorb include amino acids, bicarbonate, glucose, phosphate, proteins, and uric acid, and are thought to be associated with low ATP levels. As for which mechanism is involved, in which acquired or hereditary causes of Fanconi syndrome, they are varied and investigated. It is important to note that type 2 renal tubular acidosis is not always associated with Fanconi syndrome, but Fanconi syndrome manifests with type 2 renal tubular acidosis and excessive excretion bicarbonate.

Diagnostics

- History and physical examination.

In the history, it should be clarified whether the patient has a hereditary or acquired form. Based on this, the medical history will be narrowed. It is necessary to find out if the patient has signs, symptoms, or an official diagnosis of acquired source cystinosis, Wilson's disease, hereditary fructose intolerance, and Lowe's syndrome. You also need to find out if the patient has a history of multiple myeloma or a kidney transplant. Clinicians pay attention to the use of drugs such as valproic acid, cidofovir, adefovir, tenofovir, ifosfamide, lenalidomide, streptozocin, and ranitidine. Another acquired cause of Fanconi syndrome is acute lymphoblastic leukemia.

Physical examination may reveal excessive urinary excretion of amino acids, calcium, bicarbonate, glucose, phosphate, and uric acid. Signs that may be associated with a lack of these solutes include acidosis (due to lack of bicarbonate), dehydration, electrolyte imbalance, rickets, osteomalacia and growth impairment. Symptoms of osteomalacia include bone fractures that occur without actual injury, and widespread bone pain, especially in the hips. While hypophosphatemic osteomalacia can occur in adults, hypophosphatemic rickets can occur in children.

The loss of water and electrolytes seen during the condition can cause thirst, fatigue, weakness, and polyuria. Hypophosphatemia Causes many signs and symptoms, especially if serum phosphorus levels fall below 1 mg / dL. There may be neuromuscular symptoms such as paresthesia, tremor and muscle weakness. Severe hypophosphatemia can impair myocardial contractility, although rarely leads to clinical congestion. heart failure. Although rhabdomyolysis could theoretically be caused by hypophosphatemia, there are few reports of this association in humans.

If Fanconi syndrome is associated with cystinosis, the patient is expected to have deposition of the amino acid cystine in the bone marrow, liver, cornea (where crystals are visible), and kidneys. The patient may have a history of cystine stone formation. As a reminder, this type of stone can manifest itself in the form of a deer's antler in later stages. Otherwise, the aminoaciduria in Fanconi syndrome is likely to be minimal and not have metabolic consequences.

- Analyzes and imaging studies.

Urinalysis may show increased fractional excretion of uric acid, urinary glucose levels that are not explained plasma concentration or a pre-existing renal condition, as well as high levels of beta2-microglobulin and N-acetyl-beta-D-glucosaminidase in urine. A blood test may show hypokalemia, hypophosphatemia, and hyperchloremic (non-anionic) metabolic acidosis. A higher 24-hour urinary excretion of amino acids, phosphates, bicarbonates, and glucose may indicate a diagnosis. Some unusual tests for diagnosis include measurement of urinary retinol binding protein 4 and urine lactate to creatinine ratio, which may aid diagnosis. Measuring enzyme levels can help rule out a specific disorder, such as cystinosis, and testing levels of drugs or heavy metals in blood or urine may help detect an acquired cause of the syndrome Fanconi.

Treatment

Fanconi syndrome cannot be cured, but it can be controlled with the right treatment. Effective treatment can prevent damage to bones and kidney tissue from worsening and, in some cases, correct it. High blood acid levels (acidosis) can be neutralized with sodium bicarbonate. Patients with low blood potassium levels may require oral potassium supplements.

Bone disease requires treatment with oral phosphate supplements and vitamin D.

A kidney transplant can be life-saving if a child with this condition develops renal failurebut if cystinosis is the underlying disease, progressive damage to other organs can continue and ultimately lead to death.

If a drug is causing the condition or heavy metal poisoning is suspected, it is strongly advised to avoid or eliminate the harmful substance.

Forecast

Prognosis varies and depends on the cause of the syndrome and the severity of the renal and extrarenal manifestations. As a rule, acquired forms of Fanconi syndrome are limited in time and consequences. Inherited forms are difficult to treat, usually associated with impaired growth and affect certain organs.