Glucose - galactose malabsorption (GGM)

There are two types of genetic disorders involving the Na+/glucose cotransporters (SGLTs):

• glucose-galactose malabsorption (GGM, OMIM 182380) and familial renal glycosuria (FRG, OMIM 233100), both involving a single gene mutation
  
  
  • patients with GGM present little or no renal glycosuria at all, which is in accordance with the limited role of SGLT1 and a much larger one of SGLT2 in the kidney
  • severe diarrhoea and dehydration occur due to water retention in the intestinal lumen, caused by the osmotic loss generated by non-absorbed glucose, galactose and sodium in the intestine
  • mutations in the coding sequence of the SGLT1 gene are responsible for this disease, characterized by neonatal onset of watery and acidic diarrhea, which becomes fatal within a few weeks unless glucose- and galactose-containing nutrients are removed from the diet (1)
    
    
• FRG is a rare benign genetic condition of the kidneys characterized by an isolated defect in glucose reabsorption
  • FRG patients present various degrees of polyuria and polydipsia and the urinary loss of glucose occurs even in normoglycemia (2)
  • individuals are homozygous or compound heterozygous for an SGLT2 mutation
  • approximately 21 different gene mutations have been described for SGLT2, leading to persistent renal glycosuria, with glucose excretion of up to 160 g/day
    • at the higher level of excretion, there is a complete absence of glucose reabsorption from the glomerular filtrate
  • most cases have a SLC5A2 gene mutation (solute carrier family 5A), responsible for encoding SGLT2 transporter protein
    • autosomal dominant and recessive inheritance patterns have been reported
    • as a result of this mutation, patients with renal glycosuria excrete in their urine more than 100g of glucose in 24 hours
  • except for glycosuria, there were no other associated diseases
  • plasma glucose was high or low, and blood volume remained essentially normal due to sodium reabsorption via other transporter channels
  • renal and bladder function was normal, and this group of patients had no increased incidence of diabetes, kidney disease or urinary tract infections, compared with the general population

Reference:

• Turk E, Zabel B, Mundlos S, Dyer J, Wright EM. Glucose/galactose malabsorption caused by a defect in the Na+/glucose cotransporter. Nature 1991; 350: 354-356.
• Santer R, Kinner M, Lassen CL, et al. Molecular analysis of the SGLT2 gene in patients with renal glucosuria. J Am Soc Nephrol 2003;14:2873-82
• Elsas LJ, Rosenberg LE. Familial renal glycosuria: a genetic reappraisal of hexose transport by kidney and intestine. J Clin Invest 1969; 48: 1845-1854.