Electrolyte Alteration in Bartter Syndrome: Case Report by Tacuri Quezada Juan José in Journal of Clinical Case Reports Medical Images and Health Sciences

 Electrolyte Alteration in Bartter Syndrome: Case Report by Tacuri Quezada Juan José in Journal of Clinical Case Reports Medical Images and Health Sciences

Abstract 

Bartter syndrome is a clinical condition that presents with hyperaldosteronism, however, blood pressure is normal, this is associated with hypovolemia and high levels of PGE2. The clinical case of a pediatric patient who initially presents with significant electrolyte alterations with recurrently associated symptoms is presented. After several laboratory, imaging and genetic studies, she was diagnosed with Bartter Syndrome, for which she has been managed by several specialists. such as pediatric nephrology, genetics, and urology. The patient is currently under control and carries out her daily activities normally, under strict monitoring. It is the first clinical case of this characteristic reported in Ecuador, and contributes to those already registered worldwide, with the experience to contribute to a consensual management of this rare pathology.

Introduction 

Bartter syndrome (BS) corresponds to a hereditary disease, autosomal recessive for 5 of its variants and autosomal dominant for one of them, with 2 phenotypes and six genotypes. The estimated prevalence is 1 per million inhabitants, although in our country this type of case has not been reported in the literature. It has no predilection for race or gender. The presence of polyhydramnios without a clear cause (gestational diabetes or fetal malformations) should make you think about this pathology. (1) It is characterized by hypokalemia with normal kaliuresis, hyperreninemia with secondary hyperaldosteronism, vascular resistance to angiotensin, and overproduction of prostaglandins by the kidneys. This syndrome is rare, but is sometimes expected in patients with unexplained hypokalemia, the main difficulty being to exclude diuretic intoxication, which is very similar in all respects. Its pathophysiology is unknown and the various hypotheses raised since its description (vascular insensitivity to angiotensin, sodium or chlorine reabsorption defect, excess of atrial natriuretic factor, general anomaly of membrane permeability) have not been able to demonstrate its primary nature. , each disorder described apparently subsequently secondary to another, for this reason, treatment is difficult and disappointing, but although hypokalemia is sometimes worrying, it is usually a benign condition. (2) Previously, it had been proposed to separate “prenatal BS” (BS types I, II and IV), associated with a more severe presentation, from “classic” BS (BS type III) with a later presentation in childhood. However, recent findings have shown a wide spectrum of severity across all forms of BS: some patients with type I, II, or IV BS present with late-onset forms, while some patients with type III BS may present with with a severe prenatal presentation. (3) BS type I is genetically heterogeneous and > 63 mutations have been reported, symptoms are usually present at birth with severe salt wasting, hyposthenuria, increased production of Prostaglandin E2 and growth retardation. Some of these symptoms already occur in utero and can cause polyhydramnios and premature labor. A common feature is marked hypercalciuria, which can cause nephrocalcinosis and/or osteopenia. SB types I and II were considered prenatal variants, also called “hyperprostaglandin E syndrome,” but recent findings have shown variable phenotypic expression and severity. (4) Recently, a new mutation of the SLC12A1 gene with loss of function associated with hypokalemic metabolic alkalosis, hyperparathyroidism, hypercalcemia, nephrogenic diabetes insipidus and nephrocalcinosis has been described. The relationship between calcium and parathyroid hormone abnormalities in this different group with SLC12A1 mutations remains an unresolved issue. Early diagnosis of BS type I is mandatory because the disorder is associated with significant morbidity and mortality if not treated appropriately. 

Clinical Case

 17-year-old female patient, resident in RiobambaEcuador, student, with an oxalate-free diet, consumption of white meat, with a history of SD. Polycystic ovary managed with contraceptives for 5 months and suspended, mother with HTN. Since 2017, she had had muscle pain that was triggered after exercising plus constipation managed with laxatives. Due to this clinic, the patient went to several doctors where they performed tests, finding high levels of uric acid and hypokalemia without any known cause. She was treated with allopurinol for several months and with potassium citrate. Later (2017, April) she presented symptoms of nephrolithiasis (bilateral) and renal ultrasound imaging studies showed a number of 8 in total. The nephrolithiasis symptoms intensify, so treatment with rowatinex (antilithiasis/anethole) is started. In 2018, the urotomography showed 46 stones in the right kidney and 20 in the left (Image 1 and 2), the echo reported: left hydronephrosis. In March 2019, the patient presented muscle pain and generalized paralysis in the body, she was hospitalized and examinations showed decreased potassium, so complementary studies were initiated where levels of citrate, oxalate, uric acid, calcium and potassium were demonstrated in the urine. increased. Treatment was started with potassium citrate, Renalof and magnesium citrate, and Pregabalin was prescribed for muscle pain. In the laboratory results, he remained  with respiratory alkalosis. 08-19-22: pH 7.432 pCO2 39.4 mmHg pO2 57 mmHg HCO3-25.5 milliMoles, 05-19-22: pH 7.612, pCO2 17.6 mmHgl, pO2 154 mmHg HCO3- 22.9 milliMoles, 11-15-22: pH 7.482 pCO2 36.0 mmHg pO2 109.0 mmHg HCO: 27.1 milliMoles (metabolic alkalosis). Your kidney function urea: 26.9 mg/dl (04-06-21), creatinine: 0.62 mg/dl (04-06-21), Oxalates (Oxalic Acid) in 24-Hour Urine: 190.58 mg/24H. (07-16-19). Citrate in 24-hour urine: 2832.34 mg/24H Calcium in urine: 373 mmol/l (07-16-19), Parathyroid Hormone: 76.9 pg/mL (02-17-21). On 03/24/2021 she was hospitalized due to muscle weakness plus renal colic, showing a potassium level of 1.9. In addition, a history of serum potassium was 2.8, CL: 100, MG: 1.6, NA: 136. On physical examination she reported right lumbar pain, generalized weakness, loss of appetite, and severe stomach and digestive discomfort. Therefore, it was decided to perform genetic studies taking into account a tubulopathy, obtaining a positive result for Bartter Syndrome with a variant of uncertain significance identified in SLC12A1. SLC12A1 associated with an autosomal recessive Bartter.

Discussion

 Bartter syndrome is a rare syndrome, it consists of an autosomal recessive genetic mutation at the level of the renal tubule in the thick ascending branch of the loop of Henle, it has two forms of presentation, one prenatal and one classic (in the first years of life), is more common in pediatric age and is characterized by polyhydramnios, salt loss, hypokalemia, prematurity and metabolic alkalosis (6). However, there are cases in which this mutation occurs in adults. In a systematic review carried out from 2012- 2022, 118 patients with BS were evaluated, with a total of 57 reported cases and 9 case series with the highest concentration in Asia followed. In Europe and South America, 1 case, 66.1%, occurred in children under 5 years of age; The presentation in adults is rarer and therefore the complexity of diagnosing it, this being the second case reported in South America. (7) In these patients, BS is suspected when an adult presents unexplained hypokalemia, metabolic alkalosis and normal or low blood pressure (8), and the abuse of diuretics, laxatives, psychiatric disorders or surreptitious vomiting, which cannot be explained in an adult, has been excluded. hypokalemia. Our patient spent several years with this clinical picture consistent with electrolyte alteration (hypokalemia), nephrolithiasis, metabolic alterations and even muscular complications without reaching an early diagnosis, but after 4 years a positive result for associated SLC12A1 was identified in a genetic analysis. to an autosomal recessive Bartter. In a case report by López J, et al, indicates that, in their 14-month-old patient, the suspicion of BS arose only after having ruled out all causes of hypokalemia, and that with the usual potassium replacement treatment it was not possible. was enough, we had to resort to indomethacin (7). There is little information in the case of adults, and that indicates that it is necessary to perform a differential diagnosis between Sd. Gitelman and Sd. Bartter; Elevated calcium in urine is part of the diagnosis of BS that our patient presented with levels of 373mmol/l, which according to the literature is part of the suspicion of BS. (8) Bartter syndrome usually occurs in premature infants and polyhydramnios in most cases, but due to the inheritance of BS subtypes, adult nephrologists and pediatricians recommend the study of the variety of phenotypes across the entire age range. (9). Since the main objective of the treatment of Bartter syndrome is the correction of hypokalemia, the first-line treatment is oral supplementation with sodium chloride, potassium chloride and in some cases with drugs such as indomethacin, Potassium levels are very important, since it is the main intracellular cation and is involved in important functions maintaining normal physiology, and intra-extracellular alterations can generate alterations at the level of insulin, catecholamines, heart rate, skeletal muscle (10) and how The patient presented weakness on several occasions without focused treatment. Therefore, we consider it necessary to share and expose this case in order to improve understanding and help in the diagnosis of other cases in a timely manner.

Conclusion

 A clinical case was presented about an adult patient with electrolyte alteration and diagnosis of Bartter syndrome, in which the importance of clinical suspicion and appropriate laboratory guidance is emphasized. There are few cases reported worldwide, which makes this clinical case an important contribution to, through the description of diverse experiences, contribute to the general management of these cases.

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