title: Why is hypercalciuria absent at diagnosis in some children with ATP6V1B1 mutation?
abstract: We try to explain why hypercalciuria is absent at diagnosis in some children with an ATP6V1B1 mutation. A 5-month-old girl presented with distal renal tubular acidosis (dRTA) and sensorineural hearing loss. Direct sequencing of the ATP6V1B1 genes disclosed a new homozygous mutation (452 delT) in exon 13. In particular, an absence of hypercalciuria and a normal level of parathyroid hormones were noted. After alkaline therapy, the signs of nephrocalcinosis improved on ultrasound during follow-up. After a review of the literature regarding patients with ATP6V1B1 gene mutations, a young age seemed to be an important factor for normocalciuria. The probable mechanism of normocalciuria and a dynamic mode of calcium excretion in patients with dRTA is proposed. The determinant factors include the degree of systemic acidosis, urine pH, genetic polymorphisms, age, dietary factors, and volume status. Low sodium intake may be a major determinant of normocalciuria in these patients. It is suggested that hypercalciuria is usually absent at diagnosis of dRTA in young infants. Blood pH, plasma bicarbonate concentration, urinary citrate levels, and growth catch-up may be better indicators of adequate alkali therapy in normocalciuric children. Volume contraction, low salt content in infant formula, and alkaline urine in young infants are likely to account for the increased calcium reabsorption.
authors: Department of Pediatrics, Saint Mary's Hospital, Luodong, Taiwan.
authors: Hsin-Yun
authors: HY
authors: Tsai
authors: Shih-Hua
authors: SH
authors: Lin
authors: Chun-Chen
authors: CC
authors: Lin
authors: Fu-Yuan
authors: FY
authors: Huang
authors: Ming-Dar
authors: MD
authors: Lee
authors: Jeng-Daw
authors: JD
authors: Tsai
references: Pediatr Nephrol. 2009 Nov;24(11):2147-53
references: 19639346
references: Clin Genet. 2006 Feb;69(2):135-44
references: 16433694
references: Nat Genet. 2000 Sep;26(1):71-5
references: 10973252
references: Mol Cell Biol. 2007 Feb;27(4):1486-94
references: 17178838
references: Pediatr Nephrol. 2008 Jul;23(7):1177-81
references: 18386070
references: Kidney Int. 2001 Mar;59(3):1086-93
references: 11231364
references: Am J Physiol Renal Physiol. 2009 May;296(5):F1042-51
references: 19261737
references: Pediatr Nephrol. 2009 Jan;24(1):9-17
references: 18535843
references: Kidney Int. 1975 Oct;8(4):263-73
references: 1202255
references: Am J Kidney Dis. 2003 Jan;41(1):238-43
references: 12500243
references: Nat Genet. 1999 Jan;21(1):84-90
references: 9916796
references: Kidney Int. 2007 Apr;71(8):795-801
references: 17264873
references: Pediatr Nephrol. 2007 Jun;22(6):825-8
references: 17216496
references: Pediatr Nephrol. 2008 Jan;23(1):149-53
references: 17899212
references: J Am Soc Nephrol. 2006 Mar;17(3):617-26
references: 16421227
references: J Pediatr. 1993 Sep;123(3):393-7
references: 8355114