title: Distal RTA with nerve deafness: clinical spectrum and mutational analysis in five children.
abstract: Distal renal tubular acidosis (RTA) with nerve deafness is caused by mutations in the ATP6V1B1 gene causing defective function of the H+ -ATPase proton pump. We report five acidotic children (four males) from four unrelated families: blood pH 7.21-7.33, serum bicarbonate 10.8-14.7 mEq/l, minimum urinary pH 6.5-7.1 and fractional excretion of bicarbonate in the presence of normal bicarbonatemia 1.1-5.7%. Growth retardation and nephrocalcinosis, but not hypercalciuria, were common presenting manifestations. Hearing was normally preserved in one of the patients whose sister was severely deaf. One child was homozygous for a known mutation in exon 1: C>T (R31X). Three children were homozygous for a splicing mutation, intron 6 + 1G>A. The other patient was a compound heterozygote, having this mutation and a previously unreported mutation in exon 10: G>A (E330K). Our report shows that hearing loss is not always present in the syndrome of distal renal tubular acidosis with nerve deafness and the absence of hypercalciuria at diagnosis and describes a new mutation responsible for the disease in the ATP6V1B1 gene.
authors.affiliation: Hospital Universitario Central de Asturias, Asturias, Spain.
authors.forename: Helena
authors.initials: H
authors.lastname: Gil
authors.forename: Fernando
authors.initials: F
authors.lastname: Santos
authors.forename: Enrique
authors.initials: E
authors.lastname: García
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Alvarez
authors.forename: Flor A
authors.initials: FA
authors.lastname: Ordóñez
authors.forename: Serafín
authors.initials: S
authors.lastname: Málaga
authors.forename: Eliecer
authors.initials: E
authors.lastname: Coto
mesh_terms: D000141:Acidosis, Renal Tubular / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006130:Growth Disorders / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D009397:Nephrocalcinosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D016133:Polymerase Chain Reaction; D013577:Syndrome; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics*
chemical_list: C509766:ATP6V1B1 protein, human; D025262:Vacuolar Proton-Translocating ATPases