What is familial renal glycosuria (FRG)?

Updated: Dec 10, 2018
  • Author: Rajendra Bhimma, MBChB, MD, PhD, DCH (SA), FCP(Paeds)(SA), MMed(Natal); Chief Editor: Craig B Langman, MD  more...
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Answer

To date, only loss of function mutations have been identified in renal glucose transporters. Patients with FRG can be characterized according to the amount of glucose excreted in a 24-h urine collection, normalized for body surface: mild renal glucosuria for < 10 g/1.73 m2 per day and severe renal glucosuria for ≥10 g/1.73 m2 per day. [12]

Familial renal glycosuria (FRG) is a rare renal tubular disorder caused by mutations with the SLCA2 gene (FRG, McKusick 233100). This gene is mapped to chromosome 16p11.2. The first report of such a gene mutation was in 2000. [13] The mode of inheritance that best fits FRG has been suggested to be co-dominance with incomplete penetrance. Many heterozygous individuals display mild glycosuria (< 0.1 g/1.73 m2/24 h), others have varying degrees of glycosuria in the absence of hyperglycemia. Homozygous or compound heterozygous individuals usually have severe renal glycosuria in excess of 100 g/1.73 m2/24 h. [14, 15, 16] Some mutations retain an 80% capacity of glucose transport, whilst others completely abolish protein expression. [17]

However, not all individuals with similar or identical mutations have the same degree of increased glucose excretion, suggesting a role of non-genetic factors or other genes that may play a role in glucose transport. [18] Also other SGLTs that are known to be expressed in the kidney and whose functions have not yet been clarified are candidates for modified genes in FRG. The role of other candidate genes is also supported by the finding of at least 3 patients with FRG in whom sequencing of the entire coding region of SLC5A2 showed no mutations. [19, 20]


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