ANALISIS PSIKOLOGIS KONDISI SISWA TAMAN KANAK-KANAK SEBELUM DAN SESUDAH MENEMPATI GEDUNG TK PROGRAM PENGEMBANGAN KECAMATAN (PPK) REHABILITASI PASCA GEMPA 2006

Corresponding Author: Yudhistira Hutomo

INTRODUCTION

As a rare, autosomal recessive inherited disorder, Gitelman Syndrome may be found in 1 out of 40,000 people. The incidence is usually found in the Asian population (Kondo et al., 2021). The cause of Gitelman Syndrome was identified as a mutation in the solute carrier family 12-member 3 (SLC12A3) gene, which impairs sodium reabsorption in the distal convoluted tube (Uzunlulu & Dumanoglu, 2019). Patients with Gitelman Syndrome usually appear asymptomatic or with symptoms such as salt craving, muscle weakness, fatigue, and dizziness. Extrarenal symptoms may also appear in the form of growth retardation, thyroid dysfunction, and epilepsy (Blanchard et al., 2017; Kondo et al., 2021). Gitelman Syndrome is a form of tubulopathy that can be diagnosed during the neonatal, adolescence, and adulthood periods (Blanchard et al., 2017). Symptoms of Gitelman Syndrome appear from hypokalaemia, hypomagnesemia, and hypocalciuria, which require mandatory laboratory examination. In this case report, we present a 37-year-old woman with Gitelman Syndrome, urinary tract infection, and previous history of cesarean section.

Several studies have previously examined Gitelman Syndrome and its clinical manifestations. Kondo et al. (2021) conducted an extensive genetic study highlighting the prevalence of GS in various populations, with a particular focus on Asian cohorts, where the incidence is notably higher. Another case report by Uzunlulu et al. (2019) emphasized the electrolyte abnormalities commonly seen in GS patients, such as hypokalemia and hypomagnesemia. However, the focus was primarily on pediatric and adolescent patients, with limited cases of adult-onset GS being explored in the literature. This highlights a significant gap in understanding how the disease progresses and manifests in adult populations.

Despite extensive genetic and clinical studies on Gitelman Syndrome, there remains a gap in the documentation of adult-onset cases, particularly those presenting with atypical symptoms like urinary tract infections and a history of cesarean sections, as seen in this case. This report offers novel insights into the complexity of diagnosing GS in adult females, where the symptoms may overlap with other conditions such as pre-eclampsia and post-operative complications. Furthermore, this study emphasizes the need for a multidisciplinary approach to managing GS, combining electrolyte correction with careful monitoring of concurrent conditions.

The urgency of this research lies in the underdiagnosis and mismanagement of adult-onset GS, which can lead to life-threatening electrolyte imbalances. Given that most GS cases are identified during adolescence, clinicians may overlook or misdiagnose the syndrome in adults, leading to delayed or inappropriate treatment. This case report underscores the importance of raising awareness among healthcare professionals about the potential for GS to manifest in older patients and the need for targeted diagnostic strategies.

The primary objective of this research is to document an adult-onset case of Gitelman Syndrome and illustrate the importance of comprehensive diagnostic evaluations, including laboratory testing for electrolyte imbalances, particularly in patients with a history of cesarean section and pre-eclampsia. The research also aims to demonstrate the efficacy of electrolyte replacement therapy in managing GS symptoms. The implications of this research are far-reaching, as it can improve diagnostic protocols for adult patients with electrolyte disturbances, enhance patient outcomes through timely intervention, and contribute to the broader understanding of how GS presents across different age groups.

Case Report

Our patient was a 37-year-old woman who came to our emergency room on May 6th, 2023, with a chief complaint of fatigue. The patient stated that her symptoms just appeared on the day of admission and had not appeared previously. She felt sluggish, although both of her arms and legs were still movable, albeit weakly. She also described a loss of appetite in the last three weeks before admission. Her main complaint was accompanied by a bitter taste in her mouth, nausea, vomiting, and irregular eating habits.

Further questioning revealed that the patient underwent a cesarean section a month before her third gestation due to pre-eclampsia after spinal anesthesia. Currently, the patient is not breastfeeding her baby. The patient had no known allergy to any drugs or foods. On admission, she was overweight, with 69 kilograms (kg) and 164 centimeters (cm) of body weight and height, respectively. Vital sign measurement on admission showed a blood pressure of 140/90 mmHg, heart rate of 80 beats per minute (bpm), 20 times per minute (x/ min) of respiratory rate, and normal body temperature of 37.3oC. Neurologic examination revealed normal motoric status on both of her upper extremities but slightly reduced motoric ability on both lower extremities. Laboratory examination showed low hemoglobin (Hb) of 9.5 gram/decilitre (g/dl), elevated leukocyte of 14.15 x 103 cells/millimeter (mm)3, elevated blood sedimentation rate (BSR) of 98 mm/hour, and slightly elevated SGOT of 59 IU/L. We also discovered low sodium (115 mmol/L), potassium (1.9 mmol/L), and chloride (68 mmol/L) ion levels in this patient, suggesting an electrolyte imbalance due to low intake. No abnormalities were found in the patient’s thorax x-ray and electrocardiogram (ECG) examination results. We diagnosed the patient with suspected electrolyte imbalance and low intake. She was loaded with ringer lactate infusion and multivitamin injection, intravenous 40 mg of pantoprazole, and intravenous 8 mg of ondansetron. The internist then advised ringer lactate infusion of 500 ml per 6 hours, injection of pantoprazole 40 mg per 12 hours, injection of ondansetron 8 mg per 8 hours, and oral sucralfate 10 ml per 8 hours before hospitalization.

On the first day of hospitalization, she still felt weak and had difficulty moving her upper and lower extremities. We diagnosed the patient with dyspepsia and electrolyte imbalance. To correct her electrolyte imbalance, we administered sodium chloride 0.9% infusion of 500 ml every 12 hours with 25 milliequivalent (mEq) potassium chloride and 3% sodium chloride infusion every 24 hours. The patient was also given potassium tablets every 8 hours. We ordered thyroid stimulating hormone (TSH), free T4, and vitamin D level examination due to suspicion of thyroid disorder and periodic paralysis hypokalaemia. The patient was also scheduled for an abdominal ultrasound on the following day. On this day, we found that the patient also had a urinary tract infection. The internist then ordered to change the infusion to 3% sodium chloride 500 ml every 8 hours, injection of 2 grams ceftriaxone once a day, and re-examination of sodium, potassium, chloride, and calcium levels after electrolyte correction.

On her second day, her weakness persisted and is now accompanied by nausea, vomiting, and inability to grasp her hands and lockjaw. We changed her antibiotic injection to a 1-gram cefpirome injection every 12 hours and stopped her 3% sodium chloride infusion. Post-electrolyte correction laboratory results showed normal sodium levels but with low potassium (2.2 mmol/L) and chloride (85 mmol/L) levels. Her infusion was changed to 500 ml Ringer Lactate every 8 hours, and she was still given 12.5 mEq potassium chloride. Abdominal USG showed mild hepatomegaly with a simple cyst in her right hepatic lobe. At this point, we consulted the neurologist to evaluate any possibility of Guillain-Barre Syndrome (GBS) or other neurological disease.

The following day, the patient was able to move her extremities slightly except for both of her hands, which were still stiff. Our neurologist diagnosed the patient with tetraplegia due to hypokalaemia with a differential diagnosis of GBS. The patient was scheduled for an electromyography (EMG) examination the next day. The urinalysis result on this day was still suggestive of a urinary tract infection. We gave the patient 5000 IU of vitamin D and potassium tablet every 8 hours and planned for re-examination of electrolyte and calcium levels on the next day.

On the next day, the patient complained both of her hands were stiff and difficult to grasp. She also felt cramps in both legs every micturition. The symptoms worsened during the evening. EMG results revealed no polyradiculoneuropathy. At this point, she developed carpal spasm, which led to suspicion of Gitelman Syndrome with Bartter Syndrome as a differential diagnosis. Her urinary tract infection was declared to be treated. The patient was then given a calcium gluconate injection in 100 ml sodium chloride every hour, oral 5 mg clobazam per 12 hours, and oral vitamin D3 one tablet thrice a day. The neurologist also added 1 mg of oral lorazepam once a day. We also planned the patient for urinary tract USG as we suspected a suprarenal tumor might present and ordered an antinuclear antibody (ANA) profile, quantitative ANA, and ds deoxyribonucleic acid (DNA) examination.

On the fifth day of her hospitalization, her carpopedal syndrome persisted along with weakness, dehydrated feeling, spasms, and edema at her infusion site. Her blood pressure dropped to 90/60 mmHg, and she had low oxygen saturation (93-95%). Neurological examination showed lowered patellar reflex and positive Chvostek sign. The patient had slightly low serum calcium (8.3 mg/dl) and hypocalciuria (8.2 mg/dl). We confirmed the diagnosis as Gitelman Syndrome, hypokalaemia, hypomagnesemia, hypocalcemia, and urinary tract infection. The patient was then given an injection of magnesium sulfate (MgSO4) 2 grams in 5% dextrose 200 ml every 6 hours, an infusion of 500 ml ringer lactate every 8 hours with an injection of 25 mEq potassium chloride, oral potassium supplementation, 40 mg pantoprazole injection once a day, and 8 mg ondansetron injection every 8 hours. The neurologist administered 5 mg of clobazam twice a day. We then placed a central venous catheter on this patient. Urinary tract USG showed signs of cystitis. We also performed a blood gas analysis, which was suggestive of metabolic alkalosis.

The patient’s stiffness was starting to dissipate on the sixth day, and her vital signs were back within normal range. We still observed low potassium (2.7 mmol/L) and chloride (89 mmol/L) values; however, these values were showing improvement from previous tests. The patient’s total calcium value was still at the same value as the previous day. Vitamin D examination showed a normal value (18.74 ng/ml). We stopped the calcium gluconate and MgSO4 injection at this point. The patient’s infusion was then changed into 500 ml ringer lactate every 8 hours. The neurologist gave the patient oral 365 mg magnesium and a tablet of co-enzyme tablet once a day. The patient was then allowed to go home on the sixth day and was given oral 5 mg clobazam twice a day, a potassium tablet thrice a day, and lorazepam 1 mg once a day after showing improvement in her potassium (2.9 mmol/L) and chloride (91 mmol/L) values.

Figure 1. Diagnostic Approach to Hypokalaemia (4)

RESULTS AND DISCUSSION

We reported a case of a 37-year-old woman with Gitelman Syndrome, which was previously suspected of GBS and Bartter Syndrome. The patient, in this case, complained of general weakness, which suddenly appeared on the day of admission and was not present previously. She had a cesarean section a month before admission on her third gestation due to pre-eclampsia. Up until the third day of hospitalization, the patient did not show any neurological signs specific to the Gitelman Syndrome. It was on the following day that we found carpopedal syndrome alongside hypomagnesemia and hypokalaemia in this patient, which were signs of Gitelman Syndrome. After correcting her potassium, magnesium, and calcium levels along with the urinary tract infection, the patient showed improvement, especially in her stiffness. The patient was then allowed to go home on the sixth day of hospitalization.

Hypokalaemia and hypomagnesemia are the main findings of Gitelman Syndrome, which originates from the SLC12A3 gene. This rare autosomal recessive disorder impairs the sodium chloride transporter in the distal convoluted tube (Filippatos et al., 2018; Walsh et al., 2018). Gitelman Syndrome patients have less sodium reabsorption than healthy populations, which eventually increases potassium and hydrogen ion excretion. This condition is reflected in hypokalaemia and metabolic alkalosis in laboratory results (Urwin et al., 2020). The patient in our report was found to have hypokalaemia, hypomagnesemia, and metabolic alkalosis on her fifth day. A decrease in sodium chloride reabsorption lowers transient receptor potential channel subfamily M, member 6 (TRPM6) expression and causes magnesiuria (Filippatos et al., 2018).

Cramps or tetany and carpopedal spasms are common findings in Gitelman Syndrome. Hypokalaemia was found to be a contributing factor to tetany rather than hypomagnesemia. Short stature and drowsiness or sleepiness were also suggestive of hypokalaemia, although these signs and symptoms are more visible in children (8,9). Mutation of the SLC12A3 gene disables sodium-chloride cotransporter (NCCT) channel function, which eventually increases sodium and chloride delivery to the collecting tube and indirectly increases renin and aldosterone production. A high aldosterone level increases sodium reabsorption along with potassium and hydrogen excretion, resulting in hypokalaemia (Santra, 2023). Evaluation of potassium ion can be done by calculating transtubular K+ concentration gradient (TTKG). A TTKG value of more than four calls for an acid-base status assay. In this patient, we conducted a blood gas assay, and we found metabolic alkalosis (Umami et al., 2011). Hypokalaemia and hypochloraemia are often present in Gitelman and Bartter Syndrome. However, Gitelman Syndrome is signified by hypomagnesemia and hypocalciuria (Fulchiero & Seo-Mayer, 2019).

The patient in our case report presented herself in the emergency room with a feeling of weakness at admission. She developed stiffness in her upper and lower extremities, which eventually turned into cramps. Hypercalcemia and hypocalciuria are common findings in Gitelman Syndrome patients due to increasing calcium-ion transporters such as transient receptor potential cation channel subfamily V member 5 (TRPV5), calbindin (CALB)1, and sodium-calcium exchanger (NCX)1 (Reyes & Medina, 2022). However, in this patient, we found a slightly below-average calcium level with hypocalciuria and a normal vitamin D value. A recent case study in Poland reported an adult woman with Gitelman Syndrome and normocalciuria. The study suspected that the normal calcium value may be attributable to low aldosterone levels. Contrary to our current finding, the study found that the patient had a normal vitamin D level (Flisiński et al., 2022). Hypomagnesemia was said to hamper vitamin D activation, therefore lowering its level in the blood. Low magnesium value was also associated with decreased intestinal absorption of calcium, which may explain our hypocalcemia finding in this patient (Alnahas et al., 2022). Another manifestation of hypokalaemia and hypomagnesemia in our patient was low blood pressure (Blanchard et al., 2017).

Gitelman Syndrome often presents itself during adolescence but may also appear in older age (Uzunlulu & Dumanoglu, 2019). Some patients with Gitelman Syndrome are asymptomatic or mildly symptomatic, leading to underdiagnosis of this inherited disease (Urwin et al., 2020). A confirmed diagnosis of Gitelman Syndrome requires the identification of SLC12A3 mutation (Blanchard et al., 2017), but key clinical symptoms such as hypokalaemic metabolic acidosis, hypomagnesemia, and hypocalciuria may serve as diagnostic bases (Yu & Chen, 2020). This examination, however, was not available in our health center and, to our knowledge, in Indonesia. Differential diagnosis of Gitelman Syndrome includes diuretic and/or laxative abuse, epilepsy, ataxia, sensorineural deafness, tubulopathy (EAST) syndrome Uzunlulu et al. (2019), primary hyperaldosteronism, and Bartter Syndrome (Urwin et al., 2020). The patient, in our case, was not taking any medications and had no history of seizures. We had planned the patient for an aldosterone examination, but the patient was discharged soon after her condition improved.

Management of Gitelman Syndrome includes electrolyte correction, such as potassium and magnesium supplementation, along with aldosterone receptor antagonists, renin-angiotensin inhibitors, and other drugs (Yu & Chen, 2020). Ad libitum intake of sodium chloride is also encouraged, although its benefit is still under research. Potassium supplementation can be given in the form of potassium chloride with a starting dose of 40 mmol in divided doses per day for adults. The recommended starting dose for magnesium supplementation is 300 mg/day in slow-release tablets (Uzunlulu & Dumanoglu, 2019). In our case report, we also administered 5 mg of clobazam due to spasms, which eventually dissipated the next day, along with an improvement in her potassium and magnesium levels. The use of clobazam in Gitelman Syndrome was also reported in a past case report from Indonesia on a 13-year-old boy. The administration of clobazam in the boy was due to an underlying psychiatric condition (Prasetyo et al., 2016). We also administered 2 grams of MgSO4 to alleviate her spasms (Chakraborty & Can, 2020).

The lack of SLC12A3 examination could be considered a weakness in this case report. We were also unable to retrieve her aldosterone value before the patient was eventually discharged due to her improving condition. Although this patient was admitted with a previous history of cesarean section and urinary tract infection, we currently have not found any literature that explains the correlation between the two findings with Gitelman Syndrome.

CONCLUSION

This case of a 37-year-old woman diagnosed with Gitelman Syndrome highlights several key learning points. First, it underscores the importance of thorough diagnostic evaluations, particularly in adult patients who present with atypical symptoms, such as electrolyte imbalances, and concurrent conditions like urinary tract infections and a history of cesarean section. Early diagnosis and management, including the correction of electrolyte imbalances through potassium, magnesium, and sodium supplementation, proved effective in improving the patient's symptoms and preventing further complications.

The case also reveals the challenges of diagnosing Gitelman Syndrome in adults, as most existing literature focuses on pediatric and adolescent populations. This suggests the need for heightened awareness among clinicians regarding the potential for adult-onset GS and its overlapping symptoms with other conditions. It also calls for a multidisciplinary approach to treatment, especially in complex cases where multiple conditions coexist. Further studies are necessary to explore the presentation of Gitelman Syndrome in adult patients, particularly those with coexisting medical conditions. Research should focus on the long-term outcomes of adult-onset GS, the optimal management strategies, and the genetic factors influencing its late manifestation. Additionally, there is a need for studies that investigate the relationship between Gitelman Syndrome and other conditions, such as pre-eclampsia and post-surgical complications, to understand better how they interact and affect the course of the syndrome.

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