Saudi Journal of Kidney Diseases and Transplantation

CASE REPORT
Year
: 2010  |  Volume : 21  |  Issue : 6  |  Page : 1129--1131

Gouty arthritis in a 15-year-old girl with Bartter's syndrome


Nima Derakhshan, Dorna Derakhshan, Mitra Basiratnia, Mohammad Hossein Fallahzadeh, Ghamar Hashemi, Ali Derakhshan 
 Shiraz Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

Correspondence Address:
Nima Derakhshan
71937-Pediatric Office, Nemazee Hospital, Shiraz
Iran

Abstract

A 15-year-old girl, a known case of Bartter«SQ»s syndrome (BS) for 7 years, developed severe pain in her right knee and right and left ankle. Her older sister had BS and developed end­stage renal disease (ESRD) at the age of 14 years. Her serum uric acid was 12.6 mg/dL, 6 months ago, and 15.4 mg/dL in her recent lab data. Hyperuricemia and gouty arthritis are commonly seen in adults with BS, but to our knowledge there is no report of gouty arthritis in pediatric literature.



How to cite this article:
Derakhshan N, Derakhshan D, Basiratnia M, Fallahzadeh M, Hashemi G, Derakhshan A. Gouty arthritis in a 15-year-old girl with Bartter's syndrome.Saudi J Kidney Dis Transpl 2010;21:1129-1131


How to cite this URL:
Derakhshan N, Derakhshan D, Basiratnia M, Fallahzadeh M, Hashemi G, Derakhshan A. Gouty arthritis in a 15-year-old girl with Bartter's syndrome. Saudi J Kidney Dis Transpl [serial online] 2010 [cited 2019 Dec 8 ];21:1129-1131
Available from: http://www.sjkdt.org/text.asp?2010/21/6/1129/72305


Full Text

 Introduction



Bartter syndrome (BS) was originally described by Bartter and colleagues in 1962. [1] They repre­sent a set of closely related autosomal rece­ssive renal tubular disorders characterized by hypokalemia, hypochloremia, metabolic alkalo­sis, and hyperreninemia with normal blood pre­ssure (BP). The underlying renal abnormality causes excessive losses of sodium, chloride, and potassium in the urine. [1],[2],[3] So far, at least five genes have been linked to BS and five types of BS have been characterized. [2],[4],[5],[6],[7] The majority of patients with BS become symp­tomatic in the neonatal period but some cases in types 3 and 4 present later in adulthood. [8] Nephrocalcinosis secondary to hypercalciuria and interstitial fibrosis secondary to prolonged and intractable hypokalemia are contributing factors for chronic renal failure in BS. [9],[10],[11],[12],[13]

Hyperuricemia is another major complication of BS, which is probably secondary to de­creased clearance of uric acid associated with volume depletion and metabolic alkalosis. [13],[14]

This in turn may cause gouty arthritis. Gouty arthritis has been reported in adult patients with BS, [14],[15],[16] but to our knowledge, despite the prevalence of hyperuricemia [8],[9],[10] there is no re­port of gouty arthritis in pediatric literature. Herein, we report gouty arthritis in a 15-year­old girl, a known case of BS for 7 years.

 Case Report



An 8-year-old girl was evaluated due to fai­lure to thrive when her 14-year-old sister was found to have end-stage renal disease (ESRD). The review of pre-vious data of her sister re­vealed hypochloremic, hypokalemic metabolic alkalosis at the age of 10 years but had not been considered and not followed till she was diag­nosed with ESRD at the age of 14 years. At the age of 8 years, our patient was diagnosed as a case of BS based on clinical and labo­ratory data as follows: thin girl, weight (Wt) 17 kg, height (Ht) 115 cm, BP 80/60 mmHg.

Her laboratory findings were as follows: blood urea nitrogen (BUN) 23 mg/dL, creatinine (Cr) 1.2 mg/dL, K 2.7 meq/L, Na 140 meq/L, Cl 85 meq/L, pH 7.59 and NaHCO 3 32 meq/L. Hb 13.4 g/dL, Ca 9.4 mg/dL, P 6 mg/dL, alkaline phosphatase 934 IU, serum Mg 2.1 mg/dL, uric acid (UA) 7.5 mg/dL and 24 hour urine cal­cium 120 mg (7 mg/kg), urine Cl 55 meq/L. Kidney sonography showed increased medullary echogenicity.

Oral potassium chloride 15% and indometha­cin were started, and with a dose of 6 meq/kg/ day, her serum K was in the range of 3.4-4.1. Indomethacin was discontinued soon because of intolerance.

At the age of 13 years, her laboratory inves­tigations showed the following: BUN 24, Cr 0.9 mg/dL, K 4.3 meq/L, UA 8.5 mg/dL, HCO 3 30 meq/L, pH 7.48. Allopurinol was added to her treatment regimen. Six months later, her uric acid was still 9.2 mg/dL due to non compliance in using allopurinol. At the age of 15 years, she was referred with severe pain and swelling of right knee, right and left ankle, with a Ht of 152 cm, Wt 38 kg, Cr 1.3 mg/dL and UA 15.2 mg/dL. Her UA clearance was 0.75 mL/min and fractional clearance of UA was 2%. Colchicine was added and allopurinol was continued. Pain and swelling of joints subsided within a few days and her UA decreased to 5.2 mg/dL, 2 months following treatment. Now she is doing well on allopurinol and KCl. A hearing test con­ducted recently was normal. Parents are first cousins and meanwhile four more cases of BS had been diagnosed in their family (second cou­sins). Plasma renin activity and angiotensin and aldosterone levels were not determined and ge­netic study was not performed in this case.

 Discussion



Herein we describe a case of BS diagnosed at the age of 8 years with failure to thrive, hypo­kalemic, hypochloremic metabolic alkalosis with hypercalciuria and also increased urinary loss of potassium and chloride. Her physical and laboratory findings at presentation and a 7­year follow-up course and evolution of her hy­peruricemia to gouty arthritis are presented.

Since the initial description of BS by Bartter and his colleagues, [1] five types of BS and their responsible genes have been delineated. BS type 1 is linked to mutations of the gene SLC12A1 on chromosome 15 (15q15-q21.1). BS type 2 is linked to a gene called KCNJ1 on chromosome 11q21-25, BS type 3 (classic BS) is linked to the gene ClCNKb on chromosome 1p36, BS type 4 is linked to gene BSND on chromosome 1p31and BS type 5 is associated with activa­ting mutations of the calcium sensing receptor gene (CASR) on chromosome 3q13.3-q21. Types 1-4 are either autosomal recessive or sporadic but type 5 is autosomal dominant. [2],[4],[5],[6],[7]

In BS, types 1 and 2 are called neonatal va­riants, maternal polyhydramnios is evident from 24 to 30 weeks of gestation and the patients are usually born premature, and as newborns, they have massive polyuria of 12-50 mL/kg/hour. Life-threatening episodes of dehydration may happen in all types of BS, especially in these forms. In classic BS also, patients have a history of maternal polyhydramnios and premature de­livery. The following symptoms are common in most types of BS: polyuria, polydipsia, vomi­ting, constipation, salt craving, tendency for volume depletion, failure to thrive, and linear growth retardation. Fatigue, muscle weakness, cramps, carpopedal spasms and developmental delay may happen later in childhood in un­treated cases or patients with poor control. In untreated patients, mortality is very high be­cause of severe dehydration and also cardiac arrhythmia. [1],[2],[3] Chronic and persistent hypoka­lemia and hypercalciuria may cause interstitial fibrosis and nephrocalcinosis, respectively, and these in turn may give rise to renal insuffi­ciency. [9],[10],[11],[12],[13]

Hyperuricemia is commonly encountered in BS and as many as 50% of patients with BS have hyperuricemia. [14] Hyperuricemia is more common in American patients with BS than in Japanese despite a similar prevalence in gen­eral population in these countries. Contraction of extracellular fluid volume increases the re­absorption of sodium and uric acid at the pro­ximal tubule. Also, metabolic alkalosis may play a role in decreased renal clearance of uric acid. There are many reports of gouty arthritis in adults with BS, but to our knowledge, there is no such a report in pediatric literature. [14],[15],[16],[17]

Although we have not performed specific la­boratory investigation (angiotensin and aldos­terone levels) including genetic study in our patient, however, a late presentation or late de­tection due to lack of severe symptoms, nor­mal hearing, normal calcium and magnesium levels, indicates our case to be a type 3 BS. Type 3 BS usually presents at neonatal age but later onset is also possible. [3]

In conclusion, hyperuricemia is common in children with BS and physicians should be aware of this fact and consider serum uric acid level in periodic evaluation of children with BS for early detection and appropriate manage­ ment for prevention of gouty arthritis and also uric acid nephropathy.

References

1Bartter FC, Pronove P, Gill J Jr, MacCardLe RC. Hyperplasia of the juxtaglomerular complex with hyperaldosteronism and hypokalemic alkalosis: A new syndrome. Am J Med 1962; 33:811-28.
2Hebert SC. Bartter syndrome. Curr Opin Nephrol Hypertens. 2003;12(5):527-32.
3Deschenes G, Burguet A, Guyot C, et al. Ante­natal form of Bartter's syndrome. Ann Pediatr (Paris) 1993;40(2):95-101.
4Bichet DG, Fujiwara TM. Reabsorption of sodium chloride-lessons from the chloride channels. N Engl J Med 2004;350(13):1281-3.
5Garcia-Nieto V, Flores C, Luis-Yanes MI, et al. Mutation G47R in the BSND gene causes Bartter syndrome with deafness in two Spanish families. Pediatr Nephrol 2006;21(5):643-8.
6Scheinman SJ, Guay-Woodford LM, Thakker RV, Warnock DG. Genetic disorders of renal electrolyte transport. N Engl J Med 1999;340(15):1177-87.
7Zaffanello M, Taranta A, Palma A, et al. Type IV Bartter syndrome: Report of two new cases. Pediatr Nephrol 2006;21(6):766-70.
8Pressler CA, Heinzinger J, Jeck N, et al. Late­onset manifestation of antenatal Bartter syn­drome as a result of residual function of the mutated renal Na+-K+-2Cl- co-transporter. J Am Soc Nephrol 2006;17(8):2136-42.
9Abdel-al YK, Badawi MH, Yaeesh SA, et al. Bartter's syndrome in Arabic children: Review of 13 cases. Pediatr Int 1999;41(3):299-303.
10Rudin A. Bartter's syndrome: A review of 28 patients followed for 10 years. Acta Med Scand 1988;224(2):165-71.
11Greger R. Ion transport mechanisms in thick ascending limb of Henle's loop of mammalian nephron. Physiol Rev 1985;65(3):760-97.
12Vaisbich MH, Fujimura MD, Koch VH. Bartter syndrome: Benefits and side effects of long­term treatment. Pediatr Nephrol 2004;19(8): 858-63.
13Mantan M, Bagga A, Virdi VS, Menon S, Hari P. Etiology of nephrocalcinosis in northern Indian children. Pediatr Nephrol 2007;22(6):829-33.
14Meyer WJ 3rd, Gill JR, Bartter FC. Gout as a complication of Bartter's syndrome: A possible role for alkalosis in the decreased clearance of uric acid. Ann Intern Med 1975;83(1):56-9.
15Ogawa T, Fujise Y, Shibata S, et al. Bartter's syndrome with gouty arthritis. Intern Med 1992;31(9):1120-4.
16Moriwaki Y, Yamamoto T, Takahashi S, Tsut­sumi Z, Hada T. An atypical case of primary renal tubular hypokalaemic metabolic alkalosis with chronic tophaceous gout. Clin Rheumatol 2001;20(5):372-5.
17Yokogoshi Y, Saito S. Abnormal serum uric acid level in endocrine disorders. Nippon Rinsho 1996;54(12):3360-3.