Summary

Fanconi-Bickel glycogenosis (FBG) is a rare glycogen storage disease characterized by hepatorenal glycogen accumulation, severe renal tubular dysfunction and impaired glucose and galactose metabolism. The prevalence is unknown but less than 200 cases have been described in the literature so far. Onset occurs during the first few months of life with failure to thrive, polyuria and rickets related to proximal tubular losses. Growth retardation and hepatosplenomegaly resulting in a protruding abdomen are evident by early childhood. Puberty is delayed. Generalized osteopenia leading to fractures during childhood, with osteoporosis later in life, has also been reported. Some patients also display an abnormal fat distribution. FBG is transmitted as an autosomal recessive trait and is caused by homozygous or compound heterozygous mutations in the SLC2A2 gene (3q26.2-q27). Diagnosis may be suspected on the basis of the clinical manifestations, radiological findings revealing rickets, and from characteristic results from laboratory investigations showing proximal renal tubular dysfunction (massive glucosuria, proteinuria, phosphaturia, hypophosphatemia, aminoaciduria and hyperuricemia). However, several cases of FBG have been detected through neonatal screening of galactose levels. Additional laboratory findings include fasting hypoglycemia, ketonuria and hypercholesterolemia. Elevated serum biotinidase activity is also found in FBG patients and has recently been proposed as a diagnostic marker for this syndrome and other glycogen storage diseases. Analysis of biopsy samples reveals liver steatosis, and glycogen accumulation in the hepatocytes and proximal renal tubular cells. The diagnosis can be confirmed by identification of a mutation in the SLC2A2 gene. The principle differential diagnosis is type I glycogen storage disease, which is caused by glucose-6-phosphatase deficiency (see this term). Prenatal diagnosis is possible for families in which the SLC2A2 mutation has already been identified. Treatment of FBG is symptomatic revolving around compensation of the renal syndrome with replacement of water and electrolytes. Vitamin D and phosphate supplements are essential for preventing hypophosphatemic rickets. Patients should follow a galactose-restricted diabetic diet with fructose as the main source of carbohydrate. The long-term prognosis is unknown. The renal tubular dysfunction persists into adulthood but in most cases does not appear to progress to renal failure. Diet and supplements may alleviate some of the manifestations of FBG but do not result in improved growth, resulting in short stature in adulthood.

Expert reviewer(s)

• Pr Dominique-Charles VALLA