A novel mutation in KCNJ1 in a Bartter syndrome case diagnosed as pseudohypoaldosteronism
- 203 Downloads
Bartter syndrome (BS) is a genetic disorder with hypokalemic metabolic alkalosis and is classified into five types. One of these, type II BS (OMIM 241200), is classified as neonatal Bartter syndrome, which is caused by mutations in the KCNJ1 gene. Transient hyperkalemia and hyponatremia are usually noted in the early postnatal period, but as type II BS is a relatively rare disease, its exact clinical course and genetic background have not yet been thoroughly characterized. This report concerns a male type II BS patient with a novel mutation in the KCNJ1 gene. The unique clinical findings of this case are that hyperkalemia (8.9 mEq/l), hyponatremia, and metabolic acidosis detected in the early postnatal period led to a diagnosis of pseudohypoaldosteronism (PHA). As an adolescent, however, the patient currently shows normal potassium levels and normal renal function, although with hypercalciuria and nephrocalcinosis, without having received any treatment. In such cases, KCNJ1 mutations should be suspected. In our case, genetic analysis of the KCNJ1 gene identified a novel homozygous 1-bp deletion mutation (c.607 del. C in exon 5).
KeywordsBartter syndrome Pseudohypoaldosteronism (PHA) Hyperkalemia Hypokalemia ROMK KCNJ1
We acknowledge Ms. Yoshimi Nozu for her help in genetic analysis. This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
- 4.Simon DB, Bindra RS, Mansfield TA, Nelson-Williams C, Mendonca E, Stone R, Schurman S, Nayir A, Alpay H, Bakkaloglu A, Rodriguez-Soriano J, Morales JM, Sanjad SA, Taylor CM, Pilz D, Brem A, Trachtman H, Griswold W, Richard GA, John E, Lifton RP (1997) Mutations in the chloride channel gene, CLCNKB, cause Bartter’s syndrome type III. Nat Genet 17(2):171–178PubMedCrossRefGoogle Scholar
- 5.Birkenhager R, Otto E, Schurmann MJ, Vollmer M, Ruf EM, Maier-Lutz I, Beekmann F, Fekete A, Omran H, Feldmann D, Milford DV, Jeck N, Konrad M, Landau D, Knoers NV, Antignac C, Sudbrak R, Kispert A, Hildebrandt F (2001) Mutation of BSND causes Bartter syndrome with sensorineural deafness and kidney failure. Nat Genet 29(3):310–314PubMedCrossRefGoogle Scholar
- 6.Vargas-Poussou R, Huang C, Hulin P, Houillier P, Jeunemaitre X, Paillard M, Planelles G, Dechaux M, Miller RT, Antignac C (2002) Functional characterization of a calcium-sensing receptor mutation in severe autosomal dominant hypocalcemia with a Bartter-like syndrome. J Am Soc Nephrol 13(9):2259–2266PubMedCrossRefGoogle Scholar
- 16.Bailey MA, Cantone A, Yan, Q MacGregor GG, Leng Q, Amorim JB, Wang T, Hebert SC, Giebisch G, Malnic G (2006) Maxi-K channels contribute to urinary potassium excretion in the ROMK-deficient mouse model of Type II Bartter’s syndrome and in adaptation to a high-K diet. Kidney Int 70(1):51–59PubMedCrossRefGoogle Scholar