J Pathol Transl Med.  2016 Mar;50(2):160-164. 10.4132/jptm.2015.08.31.

An Adult Case of Bartter Syndrome Type III Presenting with Proteinuria

• Cha EJ
• Hwang WM
• Yun SR
• Park MH

• KMID: 2211384
• DOI: http://doi.org/10.4132/jptm.2015.08.31

Abstract

Bartter syndrome (BS) I-IV is a rare autosomal recessive disorder affecting salt reabsorption in the thick ascending limb of the loop of Henle. This report highlights clinicopathological findings and genetic studies of classic BS in a 22-year-old female patient who presented with persistent mild proteinuria for 2 years. A renal biopsy demonstrated a mild to moderate increase in the mesangial cells and matrix of most glomeruli, along with marked juxtaglomerular cell hyperplasia. These findings suggested BS associated with mild IgA nephropathy. Focal tubular atrophy, interstitial fibrosis, and lymphocytic infiltration were also observed. A genetic study of the patient and her parents revealed a mutation of the CLCNKB genes. The patient was diagnosed with BS, type III. This case represents an atypical presentation of classic BS in an adult patient. Pathologic findings of renal biopsy combined with genetic analysis and clinicolaboratory findings are important in making an accurate diagnosis.

Keyword

Bartter syndrome; Hypokalemia; Juxtaglomerular cell hyperplasia

MeSH Terms

Adult*
Atrophy
Bartter Syndrome*
Biopsy
Diagnosis
Extremities
Female
Fibrosis
Glomerulonephritis, IGA
Humans
Hyperplasia
Hypokalemia
Loop of Henle
Mesangial Cells
Parents
Proteinuria*
Young Adult

Figure

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  Fig. 1. Renal biopsy in a patient with Bartter syndrome with IgA nephropathy. (A) Glomerulus shows hyperplasia of juxtaglomerular cells with increased mesangial cells and matrix (periodic acid-Schiff). (B) Glomerulus shows hyperplasia and hypergranulosis of juxtaglomerular cells (Jones’ methenamine silver, × 1,000). (C) Immunofluorescence reveals weak (1+) staining for IgA in the mesangium. (D) Electron micrograph of the juxtraglomerular apparatus shows abundant progranules and mature renin granules (Hitach HT7700 EM, × 6,000).

• 

  Fig. 2. Capillary electrophoretic pattern of the multiplex ligation-dependent probe amplification products of the patient’s family. (A) The patient has a large homozygous deletion and a large heterozygous deletion. (B) Her father has a heterozygous deletion of exon 1–14. (C) Her mother has a heterozygous deletion of all examined exons of the CLCNKB gene.

Reference

1. Bartter FC, Pronove P, Gill JR Jr, Maccardle RC. Hyperplasia of the juxtaglomerular complex with hyperaldosteronism and hypokalemic alkalosis: a new syndrome. Am J Med. 1962; 33:811–28.

2. Ji W, Foo JN, O’Roak BJ, et al. Rare independent mutations in renal salt handling genes contribute to blood pressure variation. Nat Genet. 2008; 40:592–9.

3. Lee BH, Cho HY, Lee H, et al. Genetic basis of Bartter syndrome in Korea. Nephrol Dial Transplant. 2012; 27:1516–21.

4. Naesens M, Steels P, Verberckmoes R, Vanrenterghem Y, Kuypers D. Bartter’s and Gitelman’s syndromes: from gene to clinic. Nephron Physiol. 2004; 96:p65–78.

5. Xiumin W, Zheng S, Meichun X, Junfen F, Li L. A Chinese girl with Bartter syndrome type III due to a novel mutation and/or single nucleotide polymorphisms (SNPs) in CLCNKB gene. Iran J Pediatr. 2013; 23:89–94.

6. García Castaño A, Pérez de Nanclares G, Madariaga L, et al. Genetics of type III Bartter syndrome in Spain, proposed diagnostic algorithm. PLoS One. 2013; 8:e74673.

7. Simon DB, Bindra RS, Mansfield TA, et al. Mutations in the chloride channel gene, CLCNKB, cause Bartter’s syndrome type III. Nat Genet. 1997; 17:171–8.

8. Bhat YR, Vinayaka G, Sreelakshmi K. Antenatal Bartter syndrome: a review. Int J Pediatr. 2012; 2012:857136.

9. Krämer BK, Bergler T, Stoelcker B, Waldegger S. Mechanisms of disease: the kidney-specific chloride channels ClCKA and ClCKB, the Barttin subunit, and their clinical relevance. Nat Clin Pract Nephrol. 2008; 4:38–46.

10. Knoers NV, Levtchenko EN. Gitelman syndrome. Orphanet J Rare Dis. 2008; 3:22.

11. Nakhoul F, Nakhoul N, Dorman E, Berger L, Skorecki K, Magen D. Gitelman’s syndrome: a pathophysiological and clinical update. Endocrine. 2012; 41:53–7.

12. Su IH, Frank R, Gauthier BG, et al. Bartter syndrome and focal segmental glomerulosclerosis: a possible link between two diseases. Pediatr Nephrol. 2000; 14:970–2.

13. Sardani Y, Qin K, Haas M, Aronson AJ, Rosenfield RL. Bartter syndrome complicated by immune complex nephropathy: case report and literature review. Pediatr Nephrol. 2003; 18:913–8.

14. Hanevold C, Mian A, Dalton R. C1q nephropathy in association with Gitelman syndrome: a case report. Pediatr Nephrol. 2006; 21:1904–8.

15. Lee SE, Han KH, Jung YH, et al. Renal transplantation in a patient with Bartter syndrome and glomerulosclerosis. Korean J Pediatr. 2011; 54:36–9.

16. Yamamoto T, Noble NA, Cohen AH, et al. Expression of transforming growth factor-beta isoforms in human glomerular diseases. Kidney Int. 1996; 49:461–9.

17. Kömhoff M, Reinalter SC, Gröne HJ, Seyberth HW. Induction of microsomal prostaglandin E2 synthase in the macula densa in children with hypokalemic salt-losing tubulopathies. Pediatr Res. 2004; 55:261–6.

18. Pagnin E, Davis PA, Semplicini A, Calò LA. The search for a link between inflammation and hypertension: contribution from Bartter’s/Gitelman’s syndromes. Nephrol Dial Transplant. 2006; 21:2340–2.

19. Colussi G, Rombolà G, Airaghi C, De Ferrari ME, Minetti L. Pseudo-Bartter’s syndrome from surreptitious diuretic intake: differential diagnosis with true Bartter’s syndrome. Nephrol Dial Transplant. 1992; 7:896–901.