|Year : 2017 | Volume
| Issue : 2 | Page : 291-294
Gitelman syndrome: A case report of hypokalemic seizures in an adolescent male
Kristine Cornejo1, Pritiben Patel1, Swomya Bal2, Pamela L Valenza1
1 Department of Family Medicine-Warren, St. Luke's University Health Network, Phillipsburg, NJ 08865, USA
2 Department of Nephrology, St. Luke's University Health Network, Bethlehem, PA 18015, USA
|Date of Web Publication||9-Jan-2018|
Dr. Pamela L Valenza
St. Luke's Warren Family Medicine Residency, St. Luke's University Health Network, 755 Memorial Parkway, Suite 300, Phillipsburg, NJ 08865
Source of Support: None, Conflict of Interest: None
Gitelman syndrome (GS) is an autosomal recessive tubular disorder with an incidence of 1 in 40,000. It is characterized by hypokalemia, hypomagnesemia, metabolic alkalosis, with secondary hyperreninemia, which can easily be managed with a potassium (K+) sparing diuretic if correctly recognized, and with an understanding of the pathophysiology. A 17-year-old male patient presented to the emergency department after an episode of tonic-clonic seizure activity and subsequent loss of consciousness. Diagnosis of GS was made following persistent hypokalemia despite adequate repletion and further laboratory analysis. The patient was placed on a K+-sparing diuretic and had no further seizure activity. This case illustrates the importance of proper clinical and diagnostic evaluation of electrolyte abnormalities in all patients, especially in younger patients in whom early diagnosis can be crucial in preventing future complications.
The following core competencies are addressed in this article: Medical knowledge, Patient care.
Keywords: Gitelman syndrome, hypokalemia, pediatrics, seizure
|How to cite this article:|
Cornejo K, Patel P, Bal S, Valenza PL. Gitelman syndrome: A case report of hypokalemic seizures in an adolescent male. Int J Acad Med 2017;3:291-4
|How to cite this URL:|
Cornejo K, Patel P, Bal S, Valenza PL. Gitelman syndrome: A case report of hypokalemic seizures in an adolescent male. Int J Acad Med [serial online] 2017 [cited 2023 Feb 3];3:291-4. Available from: https://www.ijam-web.org/text.asp?2017/3/2/291/222472
| Introduction|| |
Gitelman syndrome (GS), also known as pure thiazide-type distal convoluted tubule (DCT) disorder or familial hypokalemia-hypomagnesemia, is an autosomal recessive disorder characterized by hypomagnesemia, hypocalciuria, hypokalemia, and metabolic alkalosis., It is caused by inactivating mutations in gene SLC12A3 on chromosome 16, which encodes for thiazide-sensitive sodium-chloride cotransporter and magnesium (Mg +2) transporter on the apical membrane of the DCT.,,,, The prevalence of GS is 1:40,000. Currently, in the literature, over 140 different loss of function mutations have been identified in GS patients.
Important differential diagnoses to consider in patients presenting with the above electrolyte abnormalities include diuretic abuse, self-induced vomiting, and Bartter Type III syndrome, which is caused by mutations in the CLCNKB gene.,, Bartter Type III syndrome presents similarly with hypokalemia and metabolic alkalosis, but with key distinguishing factors of hypochloremia, hyperreninemia, and normal blood pressure.,, In addition, patients diagnosed with Bartter Type III often present with symptoms early in infancy.
GS is typically diagnosed during adulthood during routine workups. In early childhood, patients often lack symptoms. The diagnosis of GS is determined by the presence of clinical symptoms, and serum and urine laboratory abnormalities. The severity of the disease depends on the phenotypic expression and symptomology reported by GS patients ranges from asymptomatic to paresthesias, muscle weakness, fatigue, salt craving, paralysis, or signs of neuromuscular excitability such as cramps and tetany, and rarely seizures.,, Depletion of the potassium (K+) and Mg +2 ions can affect the action potentials of cardiac myocytes and neurons potentially leading to the development of ventricular arrhythmias and seizures., Many patients suffer from low blood pressure, and some adult patients may display chrondrocalcinosis resulting from chronic hypomagnesemia. Routine cardiac and neurological screening is recommended for all GS patients. In this case, the patient is a young male with hypokalemic seizures as the primary feature of GS.
| Case Report|| |
A 17-year-old Caucasian male presented to the local community hospital's emergency department status post an episode of loss of consciousness and generalized tonic-clonic shaking witnessed by emergency medical services. Before the seizure-like activity, the patient was laying down and felt dizzy, light-headed, feverish, and he had a chronic left temporal headache sustained from an assault a few months earlier. The patient had no recollection of seizing. The patient reports approximately 1-year prior, and at the time of his assault a few months earlier, he had episodes of mild shaking/tremors and feeling lightheaded but no loss of consciousness or seizure-like activity. On both earlier occasions, he presented to the emergency department and he was found to have low K+, which was repleted, and he was released without further intervention.
On presentation, the patient had a blood pressure of 123/67, weight of 51 kg, and height of 163 cm. Examination revealed a petite habitus with a diffuse macular-papular rash with an erythematous base along his trunk and back. He appeared somnolent, however, he was oriented to person, place, and time, and was able to respond and follow commands with a Glasgow Coma Scale of 15. Bloodwork obtained was normal except a K+ level of 2.2. [Table 1] is for the remainder of the laboratory values on admission. An electrocardiogram [Figure 1] showed normal sinus rhythm, incomplete right bundle branch block, and normal QT interval. A cat scan of the head was unremarkable. In the emergency department, the patient received 60 milliequivalents (mEq) K+ and 1 L normal saline bolus.
The patient had a medical history of asthma, Kawasaki disease, and headaches, and had no pertinent surgical history, allergies, medications, or social history. Family history was positive for nephrolithiasis. The patient denied the recent history of vomiting, diarrhea, laxative, or diuretic use. The patient was admitted and underwent a magnetic resonance imaging brain, electroencephalogram, and renal ultrasound, all of which were within normal limits. Throughout the hospitalization, the patient continued to have his K+ monitored, which continued to drop, despite repletion, [Table 2]. Subsequent laboratories showed a metabolic alkalosis with pH of 7.45, bicarbonate of 30, and PCO2 of 28, as well as low Mg +2 of 1.1, and low urinary calcium. Nephrology was consulted and placed the patient on amiloride for suspected GS.
On discharge, the patient had a K+ level of 3.1 and Mg +2 of 1.5. The patient's discharge medications included the following: amiloride 5 mg daily, magnesium oxide 250 mg twice daily, and potassium chloride (KCl) 60 mEq twice daily. After discharge, the patient has had intermittent follow-up with primary care and nephrology. For 6 months, the patient stopped taking the medications and had a subsequent hospitalization for seizures with an initial K+ level of 1.9. At the time of publication, current medication regimen included amiloride 10 mg daily, magnesium oxide 400 mg twice daily, and KCl 60 mEq three times daily with a last documented K+ level of 2.3.
| Discussion|| |
The definition of hypokalemia is a serum K+<3.5 mmol/L, which can result from one of the following causes: Decreased intake, increased translocation of the ion into cells, and most often, through losses in urine, stool, or sweat. [Figure 2] illustrates the algorithm utilized to differentiate the root cause of this patient's hypokalemia. A quick and easy test designed to evaluate the driving net force for K+ secretion is the transtubular K+ concentration gradient (TTKG). In this case, the urine and serum osmolality were not ordered. Therefore the TTKG could not be calculated. Yet based on the patient's arterial blood gases, the patient was in a state of metabolic alkalosis without hypertension. In addition, the patient had hypomagnesemia, and the differentiating factor, in this case, was the hypocalciuria, which is commonly seen in GS as shown in [Table 3]. In this patient, the clinical evaluation and laboratory studies confirmed the diagnosis of GS. Genetic testing was not completed before discharge as a testing kit would have had to be requested from a university hospital.
|Figure 2: Algorithm utilized to identify the root cause of hypokalemia (Source: Umami V, et al. Diagnosis and clinical approach in Gitelman's syndrome. Acta Med Indones 2011;43:53-8).|
Click here to view
Since the tubular defect in GS cannot be corrected, the treatment regimen in these cases is aimed at minimizing episodes of hypokalemia and hypomagnesemia. In cases of symptomatic hypokalemia such as this case, a combination of amiloride (5–10 mg/1.73 m 2/day) and KCl (1–3 mmol/kg/day divided into 3–4 doses) are utilized for treatment. Given this patient had a history of multiple episodes of hypokalemia, the observation of his delayed growth could be attributed to chronic severe hypokalemia and hypomagnesemia. Adequate Mg +2 and K+ supplementation in combination with Indomethacin helps to correct growth and puberty delays. At the time of publication, genetic analysis was being pursued with continued outpatient nephrology follow-up.
| Conclusion|| |
While this case is not the first in describing seizures as a presenting clinical feature of GS, it is the first case describing both seizures and growth delay in an adolescent with GS.,, This case illustrates the importance of proper clinical and diagnostic evaluation of electrolyte abnormalities in all patients, especially in younger patients in whom the early diagnosis can be crucial in preventing future complications. This patient had presented on multiple occasions prior with hypokalemia and was treated with simple replacement, without further investigation as to the underlying cause, which could have prevented him presenting again with growth delay and seizures. GS can easily be managed with a K+ sparing diuretic if correctly recognized, and with an understanding of the pathophysiology. A detailed history, complete physical examination, exclusion of the other causes, and urine studies are crucial in helping to aid in making the diagnosis. Genetic analysis is becoming more readily available for helping identify the gene mutations, but its cost and feasibility can limit its use. Thus, importance must be placed on the clinician to recognize these abnormalities and the clinical context to pursue an appropriate work-up to help make a diagnosis and treat the patient accordingly.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
Ethical conduct of research
The authors attest that this scholarly work was conducted in accordance with the recommendations of The International Committee of Medical Journal Editors. Patient consent was obtained prior to the submission of this manuscript for publication in the International Journal of Academic Medicine.
| References|| |
Seyberth HW, Schlingmann KP. Bartter- and Gitelman-like syndromes: Salt-losing tubulopathies with loop or DCT defects. Pediatr Nephrol 2011;26:1789-802.
Knoers NV, Levtchenko EN. Gitelman syndrome. Orphanet J Rare Dis 2008;3:22.
Makino S, Tajima T, Shinozuka J, Ikumi A, Awaguni H, Tanaka S, et al
. Corrigendum to “Gitelman syndrome in a school boy who presented with generalized convulsion and had a R642H/R642W Mutation in the SLC12A3 Gene”. Case Rep Pediatr 2015;2015:853523.
Ng HY, Lin SH, Hsu CY, Tsai YZ, Chen HC, Lee CT. Hypokalemic paralysis due to Gitelman syndrome: A family study. Neurology 2006;67:1080-2.
Cruz DN, Shaer AJ, Bia MJ, Lifton RP, Simon DB. Yale Gitelman's and Bartter's Syndrome Collaborative Study Group. Gitelman's syndrome revisited: An evaluation of symptoms and health-related quality of life. Kidney Int 2001;59:710-7.
Graziani G, Fedeli C, Moroni L, Cosmai L, Badalamenti S, Ponticelli C. Gitelman syndrome: pathophysiological and clinical aspects. QJM 2010;103:741-8.
Raza F, Sultan M, Qamar K, Jawad A, Jawa A. Gitelman syndrome manifesting in early childhood and leading to delayed puberty: A case report. J Med Case Rep 2012;6:331.
Umami V, Oktavia D, Kunmartini S, Wibisana D, Siregar P. Diagnosis and clinical approach in Gitelman's syndrome. Acta Med Indones 2011;43:53-8.
Liaw LC, Banerjee K, Coulthard MG. Dose related growth response to indomethacin in Gitelman syndrome. Arch Dis Child 1999;81:508-10.
Hvelplund C, Jeppesen EM, Mortensen HB, Christiansen P. Generalized seizures as onset of Gitelman's syndrome. Ugeskr Laeger 2009;171:818.
de Luis AD, Aller de la Fuente R. Atypical presentation and diagnosis of a case of Gitelman syndrome in the adult. How to distinguish between Bartter syndrome? An Med Interna 1998;15:208-10.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]