Fanconi Bickel syndrome

Fanconi Bickel syndrome is characterized by the accumulation of glycogen in the liver and kidneys. This causes symptoms such as having weakened bones (rickets), being very small for one’s age (failure to thrive), and a specific type of kidney malfunction called renal tubular dysfunction. The accumulation of glycogen can also cause swelling of the liver and spleen (hepatosplenomegaly).^[4] Between meals, affected individuals may have low blood sugar (hypoglycemia). People with Fanconi Bickel syndrome typically enter puberty later than expected. As adults, the weakened bones may result in osteopenia or osteoporosis.^[1] Adults with Fanconi Bickel syndrome may be shorter than other people, and they may have bowed legs.^[5]

Fanconi Bickel syndrome is caused by a mutation in the SLC2A2 gene. This gene tells the body how to make a protein called glucose-transporter protein 2 (GLUT2). This protein is responsible for transporting glucose through different cells in the body. When GLUT2 is not working properly because of a mutation in SLC2A2, the body cannot transport glucose. Therefore, glucose builds up in the liver and kidneys. This glucose is stored as glycogen, and the buildup of glycogen in these body parts cause the symptoms of Fanconi Bickel syndrome.^[6]  

Fanconi Bickel syndrome is inherited in an autosomal recessive manner.^[2] This means that a person affected with Fanconi Bickel syndrome has changed (mutated) copies of both SLC2A2 genes. We inherit one copy of each gene from our mother and the other from our father. A person with only one changed copy of SLC2A2 typically does not have symptoms and is known as a carrier. The children of any two carriers have a:

• 25% chance of being unaffected
• 50% chance of being a carrier like both parents
• 25% chance of having Fanconi Bickel syndrome.^[2] 

Fanconi Bickel syndrome is diagnosed by a clinical examination that is consistent with symptoms of the condition. This clinical evaluation may reveal findings such as rickets (weakened bones) and high levels of glucose, protein, and phosphate in the urine. People with Fanconi Bickel syndrome may also have low levels of phosphate and high levels of cholesterol in the blood. People with Fanconi Bickel syndrome tend to have low blood sugar (hypoglycemia) between meals. If a diagnosis of Fanconi Bickel syndrome is suspected, it can be confirmed with genetic testing of the SLC2A2 gene.^[2]

Management of Fanconi Bickel syndrome (FBS) generally focuses on treating the signs and symptoms of the condition. For treatment of the symptoms of kidney disease, a doctor may focus on replacing the water and electrolytes that are lost from the kidneys. Additionally, vitamin D and phosphate supplements can help prevent bone weakening (rickets).^[6] 

It is recommended that people with Fanconi Bickel syndrome follow a galactose-restricted diet. Galactose is a substance that is broken down into glucose. Because people with Fanconi Bickel syndrome have trouble moving glucose throughout the body, limiting galactose prevents the buildup of glucose and glycogen in the liver and kidneys. Galactose is found in food such as milk, cheese, yogurt, and legumes. People with Fanconi Bickel syndrome should primarily eat fructose as their main carbohydrate. In addition, people with Fanconi Bickel syndrome should eat small, frequent meals in order to avoid developing low blood sugar between meals. Finally, cornstarch may be used as a substitute to provide necessary sugars to the body.^[6]

The treatments mentioned above may alleviate some of the signs and symptoms of the condition. The symptoms of kidney disease and the swelling of the liver and spleen typically resolve before adulthood. However, dietary treatments and supplements typically do not improve growth, which can result in short stature during adulthood.^[7] 

Some of the symptoms of Fanconi Bickel syndrome such as rickets can have a large effect on people’s lives. However, with the proper treatment, some of the symptoms of Fanconi Bickel syndrome can resolve with age. People with this condition have been known to reach adulthood, and there have been reports that affected individuals can have children of their own.^[7]