Introduction
Fanconi-Bickel syndrome is an uncommon autosomal recessive carbohydrate metabolism condition named after Guido Fanconi and Horst Bickel, who initially described it in 1949. Due to a fault in the glucose transporter GLUT2 encoded by SLC2A2, a glucose transport protein which, when functioning normally, allows glucose to exit several tissues, including the liver, nephrons, and enterocytes of the intestines, and enter the blood. The syndrome is characterized by hepato-renal glycogen buildup, proximal renal tubular dysfunction, and poor glucose and galactose consumption. The clinical diagnosis is supported by the presence of a pathogenic SLC2A2 variant.
What Is Fanconi Bickel Syndrome?
Fanconi-Bickel syndrome (FBS) is characterized by the deposition of a substance known as glycogen in various bodily regions. When the body needs to store glucose, glycogen is produced (sugar). Glycogen is converted back into glucose when the body requires more sugar. Glycogen is not properly stored in those with Fanconi-Bickel syndrome. Consequently, Fanconi-Bickel syndrome is referred to as a disease of glycogen storage. Glycogen specifically builds up in the kidneys and liver.
Early warning signs and symptoms include
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Developing more slowly than anticipated (failure to thrive).
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Excessive urine (polyuria).
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Weak bones (rickets).
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Children may be short-statured.
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Enlarged liver and spleen later in adulthood (hepatosplenomegaly).
What Are the Symptoms Associated With Fanconi Bickel Syndrome?
Different areas of the body may be affected by the disease's symptoms. The list of symptoms indicates which bodily systems are typically affected.
1. An abnormal accumulation of hepatic glycogen leads to alteration to the normal glycogen content in storage.
2. Failing to thrive, which means a child that fails to thrive (FTT) has noticeably below-average physical development.
3. A higher level of hepatic glycogen than usual, a rise in the volume of glycogen kept in reserve by hepatocytes.
4. Abdominal distension (abdominal enlargement).
5. Fasting hypoglycemia - Hypoglycemia is a state of having blood sugar (glucose) levels that are below normal.
6. Delayed growth - A deficiency or retardation of growth before and after birth.
7. Hepatomegaly (abnormally larger liver size).
8. Bowing of the long bones - A long bone bent or curled abnormally.
9. Increased aspartate aminotransferase content in the blood leads to disproportionately high levels of aspartate aminotransferase in the blood.
10. Nephrocalcinosis - The buildup of calcium salts in the renal parenchyma is known as nephrocalcinosis.
11. Nephropathy (kidney illness or damage).
12. Osteopenia - The abnormal bone density but not as low as osteoporosis is known as osteopenia. According to the World Health Organization, bone densitometry defines osteopenia as a T score of -1 to -2.5.
13. Doll-like faces - A facial profile is characterized by a spherical facial shape, full cheeks, a short nose, and even a small chin.
14. Liver cellular cancer - A specific type of liver tumor that develops from hepatocytes and manifests macroscopically as a tan, hemorrhagic mass in the liver.
15. Hepatic failure - Long-term inflammation that results in the scarring of healthy liver tissues and causes liver failure (fibrosis).
16. Rickets - There are two main classifications of rickets: calcipenic and phosphopenic. Both of these groups are said to frequently show hypophosphatemia. The most prevalent form of rickets, hypophosphatemic rickets, is characterized by low serum phosphate levels, resistance to Ultraviolet radiation, or vitamin D consumption. Hypophosphatemic rickets has a number of complications, including calcium, vitamin D, and phosphorus deficiency.
In addition, additional ailments such as hepatobiliary disease, intestinal, gastric, and renal disorders, as well as absorption deficiencies, can be linked to its incidence. The intensity of the symptoms might vary and are typically first noticed in childhood. Severe variants may also cause joint and bone pain, small stature, poor bone growth, and leg bowing. Low phosphate levels, hypophosphatemia, and bone mineral deficiencies are all factors in hypophosphatemic rickets. Rickets most frequently occurs as a hereditary disease.
How Is Fanconi Bickel Syndrome Diagnosed?
Clinical symptoms, radiographic evidence of rickets, and typical findings from laboratory tests demonstrating proximal renal tubular insufficiency may all be used to make a diagnosis.
Findings from laboratory tests are as follows:
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Massive glucosuria (presence of glucose in the urine).
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Proteinuria (presence of protein in the urine).
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Phosphaturia (diminished capacity to reabsorb phosphate from glomerular filtrate).
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Hypophosphatemia (low level of phosphate in the blood).
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Aminoaciduria (presence of amino acid in the urine).
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Hypouricemia (concentration less than 2.0 mg/dL of serum uric acid in the blood).
Moreover, many cases have been found because of newborn galactose screening. Fasting hypoglycemia, ketonuria, and hypercholesterolemia are further test results. Patients also have elevated serum biotinidase activity, which has just been proposed as a diagnostic indicator for this syndrome or other glycogen storage illnesses. The biopsy samples' evaluation revealed hepatic steatosis and glycogen buildup in the proximal renal tubular cells and hepatocytes. Finding a SLC2A2 gene mutation will confirm the diagnosis.
How Is Fanconi Bickel Syndrome Treated?
The treatment of rickets and acid-base disturbances are the primary focus of management, which is generally supportive. Drugs that are difficult to obtain, such as phosphate, vitamin D analogs, or even solutions to restore acid-base balance, should be obtained even locally in many underdeveloped nations. Some individuals responded well to treatment, with improvements in their acidity and rickets symptoms, although long-term monitoring is required to fully assess their growth and puberty. The likelihood of surviving adulthood is high, as shown in one case report with normal fertility. While a late diagnosis complicates the situation and raises mortality, mainly due to lung infections or liver failure, as shown in certain documented cases, early recognition and effective therapy may result in a better prognosis.
Conclusion
Fanconi-Bickel syndrome is an autosomal recessive condition that usually manifests in the first few months of birth. Genetic counseling is advised for affected families. While both parents were unaffected carriers, there is a 25 percent chance that their children may inherit the illness. Growth retardation, partially offset by delayed puberty. The glomerular filtration rate is either normal or slightly reduced. A unique pattern of decreased proximal tubular transport mechanisms, involving a notable reduction of glucose transport, characterizes renal tubular dysfunction. Galactose and glucose utilization are defective, although fructose metabolism appears to be in the usual range. The liver's glycogenosis could be an epiphenomenon. The kidney's proximal tubule is the only place where glycogen builds up, with levels peaking in the straight section. The complicated abnormalities of renal tubular transit and various types of glycogenosis characterize the Fanconi-Bickel syndrome as a distinct clinical entity from those other inherited metabolic illnesses. Early diagnosis and prompt treatment result in a savior of this disease.
