ESPE Abstracts

Brother 1: 7 years old boy, with right genu valgum and short stature (−2,11 DS); X ray shows rickets features. Plasmatic Calcium 9.3 mg/dl; phosphate 2.5 mg/dl; Alkaline phosphatasas 460 U/l; Parathyroid hormone 83 pg/ml; 25OH Vitamin D 24 ng/ml. Urine calcium 159 mg/24 h (9.2 mg/K per day); Urine phosphate 870 mg/24 h; TmP/GFR 2.6 (NV:3.8 −5.0); proteinuria 100 mg/dl.

Brother 2: 4 y.o boy with frequent respiratory diseases in infant period. Genu valgum from 3 years old. Short stature (−3.08 DS) and BMI p16. Rachitic rosary and wide metaphysis. Normal calcium; Phosphate 2.8 mg/dl; Alkaline phosphatasas 742 U/l; Parathyroid hormone 155 pg/ml; 25OH Vitamin D 5.4 ng/ml. Urine calcium 210 mg/24 h (17 mg/K per day) – Urine phosphate 670 mg/24 h – TmP/GFR 1.9 (NV:3.8 −5.0); proteinuria 110 mg/dl. Renal ultrasound with nephrocalcinosis.

Brother 3: Healthy boy until 10 y.o when start genu valgum. He has mild hypophophatemia and hypercalciuria. The initial treatment of Colecalciferol normalized PTH. Then, they receive phosphate and citrate salts and thiazide diuretics until now; plasma Phosphate increased. Genu valgum partially improved. They still had good renal function. The genetic study identified the mutation c.731C>T (p.S244L) in CLCN5 gen in the 3 brothers. The mother is an asyntomatic carrier. The father has not the mutation. (done by the RenalTube project, and Instituto Salud Carlos III and Fondo Europeo Desarrollo Regional “Una manera de hacer Europa” and Asdent)

Discussion: Dent’s Disease is a X-linked inherited renal tubular disorder characterized by manifestation of proximal tubular dysfunction, including proteinuria, hypercalciuria, nephrolitiasis, nephrocalcinosis and progressive renal failure. Rickets occur in a minority of patients. The disease is found in males, generally in early childhood. Female carriers are asyntomatic or show a very mild phenotype. It is caused by mutations in either CLCN5 (Dent’s disease1) or OCRL1 (Dent’s Disease2) genes located on chromosome Xp11.22 and XQ25 respectively. CLCN5 encodes the electronic CL−/H+ CIC-5 and it is inactivation is associated with severe trafficking defect in tubular cells. Treatment is supportive, with focus on prevention of nephrolithiasis. Thyazides diuretics are used to treat hypercalciuria. In case of rickets must use phosphate suplements and Vitamin D must be used with caution since it may increase hypercalciuria. High citrate diets seem to delay progresión of renal disease.