We report the identification of a mutation in the solute carrier family 5 member 2 (SLC5A2) gene, which encodes sodium-glucose cotransporter 2, in a family with familial renal glucosuria. The proband was a 26-year-old Japanese man referred to the diabetes division with repeated glucosuria without hyperglycemia. His mother, uncle and grandfather also had a history of glucosuria. A heterozygous missense mutation (c.303T>A: p.N101K) in SLC5A2 was identified in the patient and his mother, but not in 200 chromosomes from 100 healthy and unrelated individuals, or in 3,408 Japanese individuals in the Tohoku Medical Megabank. Furthermore, bioinformatics software predicted that this lesion would be pathogenic. We infer that the mutation led to clinically relevant sodium-glucose cotransporter 2 dysfunction. The patient showed no symptoms of hypoglycemia, but continuous glucose monitoring confirmed asymptomatic hypoglycemia.

Objective:Although primary aldosteronism (PA) worsens quality of life (QOL), there have been no reports on whether treatment with a mineralocorticoid receptor antagonist (MRA) improves QOL in Japanese PA patients. Using the 36-Item Short-Form Health Survey (SF-36), we compared the QOL of PA patients before and after treatment and evaluated whether the effectiveness of MRAs differs by sex and serum potassium level.Methods:In 50 patients diagnosed with PA (with or without hypokalemia) and treated with an MRA, the SF-36 scores, blood pressure, and clinical features were assessed before, and 3 and 6 months after treatment. Separate analyses were also conducted for males and females, and for those with and without hypokalemia.Results:MRAs decreased systolic blood pressure (140.6 ± 2.4 mmHg and 125.1 ± 1.2 mmHg, p < 0.01) and increased serum potassium (3.8 ± 0.1 mEq/L and 4.2 ± 0.1 mEq/L, p < 0.01) and active renin levels (3.2 ± 0.4 pg/mL and 7.9 ± 1.2 pg/mL, p < 0.01) in PA patients. The normative mean SF-36 score of the healthy subjects was 50. The pre-treatment Role-Physical (RP) (46.7 ± 1.8, p = 0.019), General Health (47.1 ± 1.3, p = 0.042), and Role-Emotional (47.2 ± 1.7, p = 0.045) SF-36 subscale scores of all PA patients were significantly lower than those of healthy subjects but were improved by MRA treatment. Females with PA had a lower RP score (45.1 ± 2.2, p < 0.01), which was not improved by MRA treatment (46.1 ± 2.4, p = 0.036). In addition, PA patients with hypokalemia had a lower Mental Health SF-36 subscale score (43.2 ± 4.4, p = 0.041), which was improved by treatment with an MRA.Conclusions:MRAs improved the QOL of Japanese PA patients and were also effective for treating PA patients with hypokalemia, but female PA patients may be more resistant to MRAs.