Clinical features of pediatric renal glucosuria cases due to SLC5A2 gene variants

Abstract

Background Familial renal glycosuria (FRG) is a rare renal tubular disorder characterized by a variable loss of glucose in the urine despite normal blood glucose levels, which is seen in a condition in which other tubular functions are preserved. In this study, the molecular and clinical characteristics of pediatric FRG cases due to SLC5A2 gene variants were defined. Methods Demographic features, diagnostic tests, and molecular analyses of patients with a diagnosis of FRG cases due to SLC5A2 gene variants were retrospectively analyzed between 2016 and 2019. Results The data of 16 patients who were clinically and genetically diagnosed with FRG in a 4‐year period were analyzed. Seven (44%) of the cases were female and 9 (56%) were male. The median age at diagnosis was 6 years old (2 months old to 17 years old). Neuromotor development was found to be appropriate for the age in each case. Systemic blood pressure was evaluated as normal. A homozygous pathogenic variant in the SLC5A2 gene was detected in 14 patients in the genetic examination. A heterozygous variant was detected in one patient. In the other patient, two different heterozygous pathological variants were found in the SLC5A2 gene. Conclusions It was revealed that growth and development were normal in children with glucosuria due to variations in the SCL5A2 gene. Renal function tests and urinary amino acid excretion were also within normal values. In our case series, the most common genetic variation in the SCL5A2 gene was the A219T (c.655G>A) variant.

Performance of the ACMG‐AMP criteria in a large familial renal glucosuria cohort with identified SLC5A2 sequence variants

“…SGLT2 accounts for most of glucose reabsorption in the renal proximal tubule. 4 Several other FRG cohorts have been studied, listed and updated in 2019 5 with a few additional reports meanwhile published, 6,7 that further established FRG as a co-dominantly inherited phenotype instead of a recessive one, as initially assumed. Individuals harboring two in trans SLC5A2 mutations typically display urinary glucose excretion (UGE) in excess of 10 g/1.73 m 2 /day.…”