1/16. mutation analysis of the GLUT2 gene in patients with Fanconi-Bickel syndrome. Fanconi-Bickel syndrome (FBS) is an autosomal recessive disorder manifesting hepatorenal glycogen accumulation, Fanconi nephropathy, and impaired utilization of glucose and galactose. Several mutations in a gene encoding a glucose transporter, GLUT2, have recently been reported in patients with FBS. We performed molecular analysis on three Japanese patients and found four novel mutations: a splice-site mutation (IVS2-2A>G), a nonsense mutation (Q287X), and two missense mutations (L389P and V423E). Heterozygotes of L389P or V423E mutation from the patients' families showed renal glucosuria. These data suggested that GLUT2 gene defects may be a cause of renal glucosuria. ( info) |
2/16. Identification of a novel form of renal glucosuria with overexcretion of arginine, carnosine, and taurine. Glucosuria occurs in diabetes mellitus, generalized proximal tubular dysfunction of Fanconi's syndrome, glucose-galactose malabsorption syndrome, and primary renal glucosuria. patients with primary renal glucosuria have normal blood glucose levels, normal oral glucose tolerance test results, and persistent glucosuria that may approach the filtered load of glucose in the most severe cases. The primary defect is proposed to be in the sodium-glucose cotransporter type-2 (SGLT2) located in the apical membrane of S1 segment proximal renal tubule cells. Primary renal glucosuria is classified as types A, B, or O based on the characteristics of the transport defect. The magnitude of glucosuria has varied from 20 to 150 g of glucose excreted in 24 hours. Described inheritance patterns have included both autosomal dominant and autosomal recessive mechanisms. Some cases have been associated with selective aminoaciduria, distinctly unlike the generalized aminoaciduria seen in Fanconi's syndrome. We report the first case of primary renal glucosuria with selective overexcretion of arginine, carnosine, and taurine. This case may represent a genetic defect unique from the abnormalities in previously described cases of primary renal glucosuria with different amino acid excretion patterns. Future investigations could determine whether the syndrome involves a defect in the SGLT2 gene. ( info) |
| glycosuria was detected in a 37-year-old Chinese woman by a urinary examination in a local clinic with clinical evidence of acute pyelonephritis (APN). Transient glycosuria is an unusual complication of acute pyelonephritis in non-diabetic patients. As there is growing prevalence of type 2 diabetes in the population worldwide, it must be recognized that mistaken diagnosis of diabetes mellitus by glycosuria may predispose patients to an unfavorable hypoglycemic episode. Thus definite diagnosis of diabetes mellitus should be made only after recovery of APN by means of urinalysis or by simultaneous blood glucose concentration analysis. ( info) |
| Renal glycosuria associated with the use of angiotensin-converting enzyme inhibitors has been previously reported in two patients. A third patient was studied who developed isolated glycosuria associated with lisinopril therapy. As in the two previously described patients, this patient had a normal serum glucose level, underlying hypertension, and onset of glycosuria between 2 and 16 weeks after initiation of therapy with an angiotensin-converting enzyme inhibitor. The patient had renal artery stenosis with elevated renin levels. Age, time until resolution of glycosuria, and a rise in serum creatinine level did not have a consistent relationship with glycosuria associated with angiotensin-converting enzyme inhibitor therapy. Since glycosuria was the only defect noted, without evidence of any other urinary solutes, angiotensin-converting enzyme inhibitors may exert an effect on the glucose-specific proximal tubule transport system. ( info) |
5/16. hypercalciuria in children with renal glycosuria: evidence of dual renal tubular reabsorptive defects. During the past 5 years, we have identified idiopathic hypercalciuria in five of seven patients referred for evaluation of renal glycosuria between 1985 and 1991. The children, all boys, ranged in age from 6 to 12 years. Endocrine function was normal, and none of the patients had hyperparathyroidism, hypercalcemia, renal tubular acidosis, or other secondary causes of hypercalciuria. The calcium/creatinine ratio in a fasting urine specimen was elevated in all five children who had hypercalciuria, with a mean value ( /- SD) of 0.34 /- 0.06 (normal, < 0.2). In one child who had renal colic with spontaneous passage of gravel-like material, the idiopathic hypercalciuria persisted after 1 week on a diet containing 2000 mg of sodium and 300 mg of calcium. On the basis of studies that examined the site along the nephron responsible for hypercalciuria in rats with streptozocin-induced diabetes, we speculate that in children with renal glycosuria, there is defective reabsorption of glucose and calcium in the straight portion of the proximal tubule or in the collecting duct. It is likely that a similar mechanism accounts for the idiopathic hypercalciuria in children with diabetes mellitus. ( info) |
6/16. Novel compound heterozygous mutations in SLC5A2 are responsible for autosomal recessive renal glucosuria. Familial renal glucosuria is an inherited renal tubular disorder. A homozygous nonsense mutation in the SLC5A2 gene, encoding the sodium/glucose co-transporter SGLT2, has recently been identified in an affected child of consanguineous parents. We now report novel compound heterozygous mutations in the son of non-consanguineous parents. One allele has a p.Q167fsX186 mutation, which is expected to produce a truncated protein, and the other a p.N654S mutation involving a highly conserved residue. These findings confirm that mutations in the SLC5A2 gene are responsible for recessive renal glucosuria. ( info) |
7/16. Renal glucosuria due to SGLT2 mutations. Isolated renal glucosuria results from mutations in SGLT2, which codes for an active transporter specific for d-glucose and expressed in the luminal membrane of the renal proximal tubule. In affected individuals, glucosuria leads to pursuit of hyperglycemia to exclude defects in glucose metabolism, and to investigation of renal proximal tubular function to exclude renal fanconi syndrome. Here we present clinical and molecular data regarding a 19-year-old woman with isolated glucosuria. She was compound heterozygous for two SGLT2 mutations, i.e., a new missense mutation, T200K, and a known missense mutation, N654S. ( info) |
| Massive immune hemolysis due to passenger lymphocyte-derived anti-D has not been reported in renal transplantation. A 50-year-old (B-positive) male received a dual deceased-donor kidney transplant (B-negative) for diabetic renal failure. Two weeks post-transplant, the patient developed severe hemolytic anemia. The donor anti-D titer was 1:8. The recipient anti-D titer (zero pre-transplant) increased from 1:4 to 1:16 over 4 days. Rapid hemolysis caused severe anemia, minimum Hb = 4.2 g/dL, while selectively lysing the patient's autologous red cells during this time. The hemolytic anemia did not impair the allografts and subsided without monoclonal B-cell pharmacotherapy or apheresis. The anti-D titer decreased to barely detectable levels at four months and had cleared when checked 2 years post-transplant. Transfusion support subsided after two months. If complications of anemia can be avoided, the deleterious effects of hemolysis may be well tolerated by renal allografts using antigen negative transfusion alone. ( info) |
9/16. Familial renal glucosuria: SLC5A2 mutation analysis and evidence of salt-wasting. Familial renal glucosuria (FRG) is an inherited renal tubular disorder characterized by persistent isolated glucosuria in the absence of hyperglycemia. Mutations in the sodium/glucose co-transporter SGLT2 coding gene, SLC5A2, were recently found to be responsible for the disorder. Here, we report the molecular and phenotype study of five unrelated FRG families. Five patients were identified and their family members screened for glucosuria. SLC5A2 coding region of index cases was polymerase chain reaction amplified and sequenced. Five different mutations are reported, including four novel alleles. The IVS12 1G>A and p.A102V alleles were identified in homozygosity in index patients of two unrelated families. A proband from another family was compound heterozygous for the p.R132H and p.A219T mutations, and the heterozygous p.Q167fsX186 frameshift allele was the only mutation detected in the affected individual from an additional pedigree. For the remaining family no mutations were detected. The patient homozygous for the p.A102V mutation had glucosuria of 65.6 g/1.73 m(2)/24 h, evidence of renal sodium wasting, mild volume depletion, and raised basal plasma renin and serum aldosterone levels. Our findings confirm previous observations that in FRG, transmitted as a codominant trait with incomplete penetrance, most mutations are private. In the only patient with massive glucosuria in our cohort there was evidence evocative of renin-angiotensin aldosterone system activation by extracellular volume depletion induced by natriuresis. Definite proof of renin-angiotensin aldosterone system activation in FGR should rely on evaluation of additional patients with massive glucosuria. ( info) |
10/16. Type O renal glucosuria. We observed a 7-year-old boy with virtual absence of renal tubular glucose reabsorption (type O renal glucosuria). Glucose titration studies in his family revealed severe type A renal glucosuria in a younger brother, a mild type A defect in the mother and normal glucose reabsorption in the father; thus a spectrum of renal glucose transport defects was observed in members of the same family. ( info) |