SLC2A2 gene
Also known as: Glycogen Storage Disease XI;Toni-Debré-Fanconi syndrome; Hepatorenal glycogenosis with renal Fanconi syndrome; Hepatic glycogenosis with Fanconi Nephropathy; Hepatic glycogenosis with amino aciduria and glucosuria; Fanconi Syndrome with intestinal malabsorption and galactose intolerance; Pseudo-Phlorizin Diabetes; Glycogenosis, Fanconi Type – GSD XI
OMIM#227810 https://omim.org/entry/227810
1. The Disease:
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.
2. The Symptoms:
Onset occurs during the first few months of life with failure to thrive, polyuria (increased amount of urine), normo/hypokalemic metabolic acidosis (leads to potassium levels “K”), fasting hypoglycemia and post-feeding hyperglycemia. Metabolic acidosis, hypokalemia (low K), 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.
3. Actions to take in case of early diagnosis:
- Infants with a positive genetic test (having 2 pathogenic variants or 2 copies of a single pathogenic variant in the SLC2A2 gene) should continue breastfeeding, avoid fasting. Early treatment is essential in preventing chronic symptoms.
- In some cases, biochemical NBS can give some clues, as increased galactose levels and biotinidase activity.
- GSD XI is a lifelong disease that requires regular evaluation by a metabolic physician and metabolic nutritionist to avoid fasting, and follow a specific diet to prevent hypoglycemia and ketosis.
- 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 description of the first identified and treated patient reveals that renal function is preserved in adulthood despite renal tubular dysfunction and liver involvement also persisting.
- Genetic counseling is highly recommended for family planning and evaluation of at-risk family members such as siblings.
4. For more information
Biblio:
- Sharari S, Abou-Alloul M, Hussain K, Ahmad Khan F. Fanconi-Bickel Syndrome: A Review of the Mechanisms That Lead to Dysglycaemia. Int J Mol Sci. 2020;21(17):6286. PMID: 32877990.
- Mohandas Nair K, Sakamoto O, Jagadeesh S, Nampoothiri S. Fanconi-Bickel syndrome. Indian J Pediatr. 2012;79(1):112-114. PMID: 21327337.