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A rare glycogen storage disease due to a deficiency in solute carrier family 2, facilitated glucose transporter member 2 and characterized by hepatorenal glycogen accumulation leading to severe renal tubular dysfunction and impaired glucose and galactose metabolism.
ORPHA:2088Classification level: Disorder
- GSD due to GLUT2 deficiency
- GSD type 11
- GSD type XI
- Glycogen storage disease due to GLUT2 deficiency
- Glycogen storage disease type 11
- Glycogen storage disease type XI
- Glycogenosis due to GLUT2 deficiency
- Prevalence: Unknown
- Inheritance: Autosomal recessive
- Age of onset: Infancy, Neonatal
- ICD-10: E74.0
- OMIM: 227810
- UMLS: C3495427
- MeSH: -
- GARD: 2268
- MedDRA: -
The prevalence is unknown but less than 200 cases have been described in the literature to date.
Onset occurs during the first few months of life with failure to thrive, polyuria, normo/hypokalemic metabolic acidosis, fasting hypoglycemia and post-feeding hyperglycemia. Metabolic acidosis, hypokalemia, hypophosphatemia and rickets are the consequence of severe proximal tubule dysfunction. Growth retardation and hepatosplenomegaly resulting in a protruding abdomen are evident by early childhood. Puberty can be delayed. Generalized osteoporosis can lead to fractures already during childhood. Some patients also display an abnormal fat distribution.
The disease is due to homozygous or compound heterozygous mutations in the SLC2A2 gene (3q26.2-q27), encoding the protein, solute carrier family 2, facilitated glucose transporter member 2.
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 hypouricemia). However, several cases 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 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. The renal phenotype must be differentiated from other forms of genetically determined Fanconi Syndrome.
Prenatal diagnosis is possible for families in which the SLC2A2 mutation has already been identified.
The pattern of inheritance is autosomal recessive and genetic counseling is recommended for affected families. The risk of offspring inheriting the disease is 25% where both parents are unaffected carriers.
Management and treatment
There is no causal treatment. Therapy consists of replacing water and electrolytes lost through urine excretion as a result of the proximal tubule dysfunction. In addition, Vitamin D replacement is also fundamental for preventing hypophosphatemic rickets. Patients should follow a galactose-restricted diabetic diet with fructose as the main source of carbohydrate. During infancy, night feeding can be necessary in order to avoid hypoglycemia.
The long-term prognosis is unknown. However, the description of the first identified patients reveals that renal function is preserved in adulthood despite renal tubular dysfunction and liver involvement also persisting.