Analysis of Hospitalized Geriatric Patients From an Emergency Department

Introduction: The increase in the geriatric population in industrialized countries also increases the rate at which this group utilizes emergency services. Evaluation of this patient group is not specific to a single discipline, but requires a multidisciplinary approach. Information obtained by examining emergency service use among geriatric patients can inform us of approaches to improve hospital efficiency and potentially reduce the morbidity and mortality rates. Metarial and Method: This study investigated the retrospective records of geriatric patients who presented to emergency services during 2016 XXXTraining and Research Hospital, Turkey. Demographic characteristics, diagnoses, hospitalization rates, hospitalization according to clinics, seasonal characteristics, duration of hospital, and patient outcomes were evaluated. Study data were evaluated using the SPSS 20.00 statistical program. Results: A total of 314.178 patients opted for emergency services during 2016, and 29.163 (9.2%) were 65 years old and older. Among these patients, 10.545 were hospitalized, of whom 4.246 (40.2%) were aged 65 years or older. The most frequently utilized hospital units were the cardiology (n = 723, 17.02%), the neurology (n = 717, 16.88%), and the chest diseases (n = 674, 15.87%). Discussion and Conclusion : The geriatric population requires that necessary changes should be made in healthcare structures. Our study, which evaluates hospitalization rates and health status in geriatric population at a provincial which can also provide a regional level, can help in making patient admission, follow-up, and rehabilitation more comprehensive

Can Cardiac Arrhythmia Risk Be Predicted By Evaluating The Electrocardiographs Of Patients Diag- nosed With Chronic Obstructive Pulmonary Disease Exacerbation In The Emergency Department?

Can Cardiac Arrhythmia Risk Be Predicted By Evaluating The Electrocardiographs Of Patients Diagnosed With Chronic Obstructive Pulmonary Disease Exacerbation In The Emergency Department?Murtaza Kaya1, Harun Yildirim1, Abdil Coskun2, Hasan Aydin2, Esref Genc2, Emine Kadioglu1 1Kutahya Healthy Sciences University, Medical Faculty, Department of Emergency Medicine, Kutahya, Turkey 2Kutahya Evliya Celebi Training and Research Hospital, Emergency Servises, Kutahya, TurkeyIntroduction: According to data from the World Health Organization, chronic obstructive pulmonary disease (COPD) accounted for 5% (3.7 million) of deaths across the world in 2015. On the contrary, the total number of patients reached 251 million in 2016 (1). When the causes of death in this group are examined, it is two to three times higher than the deaths due to sudden cardiac arrest in the normal population (2). Studies have shown that cardiac repolarization and increasing dispersion in patients with COPD cause malignant ventricular arrhythmia and sudden cardiac deaths (3–4). It has been observed in the follow-up of patients with COPD that various pathophysiological mechanisms—such as increasing ventricular afterload, right ventricular hypertrophy, and structural changes affiliated with emphysema—cause electrocardiographic (ECG) changes (5). Existing studies show that there is much greater arrhythmia risk in the case of acute COPD attacks (6–7). These arrhythmias generally arise as the result of abnormal atrial and ventricular repolarization depending on the increasing automaticity, which occurs at the conclusion of increased exacerbation and hypercapnia that is dependent on the changes in oxygen, carbon dioxide, and pH (8–9).Detecting ECG changes in patients diagnosed with COPD acute exacerbation may play an important role in patient outcome. When evaluating cardiac repolarization disorders, it should be kept in mind that COPD exacerbation may also disrupt the cardiac rhythm.In this study, we aimed to predict the possibility of arrhythmia by comparing the ECG changes of patients admitted to the emergency service for acute COPD attacks.Material And MethodsStudy Design and ParticipantsPatients who were admitted to a tertiary emergency department with dyspnea and diagnosed with COPD acute attack between 01.01.2019-30.06.2019 were included in this study. A total of 709 patients identified as R06.0 according to the tenth revision of the International Classification of Diseases were retrospectively analyzed in this study. In this treatment group, 536 patients who did not have a follow-up concerning COPD before the application date were excluded from the study, and the emergency service follow-up file of 173 patients was looked into. Twenty-two patients whose ECG could not be reached and 85 patients whose artifact and arrhythmia were determined in their ECG were excluded from the study. Sixty-six patients whose data could be reached and evaluated as acute were included (Figure 1). Fifty-four individuals not having any complaint about the respiratory 534STtract and not diagnosed with any cardiac pathology (who had their ECG performed to exclude these pathologies) were included in the study as the control group for the same period. The demographic features (age and gender), ECG parameters (P wave, QT interval, and T wave peak–end duration [Tpe]), and electrolyte parameters (sodium and potassium) of the two groups included in the study were analyzed. The study was approved by the Noninvasive Ethnic Group of XXXX (March 17, 2021/05-12).ECG Evaluation: After 12-lead ECG pictures of the patients taken using a smartphone and uploading these pictures to a computer, an experienced emergency medicine physician evaluated them (Figure 2). The ECG records of all the patients included in the study were procured using a MAC800 (2017) device. These ECG pictures were taken at a speed of 25 mm/s and at an amplitude of 10 mm/mV. After calculating the maximum (max) duration in the longest lead and the minimum (min) in the shortest lead in ECG parameters, the dispersion (disp) durations were determined by the difference of the maximum and minimum values. The QT interval was defined as the time from the beginning of the QRS complex to the end of the T wave. Also, using the Bazett formula and calculating the variation of corrected QT (QTc) was obtained. The distance between the peak (Tp) of the T wave and the isoelectric line and even the last endpoint (Tp-e) was calculated using the tangent method (10). QT max, QT min, QT disp, QTc max, QTc min, QTc disp, Tp-e max, Tp-e min , Tp-e disp and P max, P min, P disp were calculated. Tp-e/QT and Tp-e/QTc proportions were included in the dataset by calculating these proportions.Statistical Analysis: SPSS (v.20.0; IBM Corp., Armonk, NY, USA) was used to perform all statistical analyses. Normality of the data was tested using the Kolmogorov–Smirnov test. Numeric variables indicating normal distribution were represented as mean ± standard deviations (SDs); abnormally numeric variables as median (interquartile ranges [IQRs]); and categorical variables as numbers and percentages. Student’s t test was used for numeric variables with normal distribution, and Mann-Whitney U test was used for abnormally distribution. The chi-squared or Fisher exact test was used for categorical variables. Receiver operating characteristic (ROC) analysis was performed for values with significant differences between groups. A four-cell chart had been created after the cutoff time, which was specified using the Youden Index. Sensitivity, specificity, positive (PPV) and negative predictive value (NPV), and positive likelihood (LR+) and negative likelihood (LR−) proportions were measured. A p-value <0.05 was considered statistically significant.Results: A total of 120 patients were included in the study, with 66 in the COPD group and 54 in the control group. Forty-eight (64%) of the males included in the study were in the COPD group and 27 (60%) in the control group, whereas 18 (40%) of the females were in the COPD group and 27 (60%) in the control group. It was found that there was more COPD in men than women in the study groups (p = 0.011). The mean age in the COPD group was 68.5, while it was 66.5 in the control group. There was no significant difference between the two groups (p = 0.189). According to the electrolyte parameters, the mean levels of sodium in the COPD and control groups were 140 mmol/L and 140  mmol/L, while  the mean levels of potassium were 4.1 mmol/L and 4.2 mmol/L, respectively. There wasn’t a statistically significant difference the electrolyte values between two groups (p= 0.353, p= 0.071). Results are detailed in Table 1.ECG parameters were evaluated in milliseconds (ms). In the control and study groups, the median QT max was 360 ms and 400 ms; the QT min was 300 ms and 320 ms; and QT disp was 40 ms and 535ST40 ms. There was a significant difference between QT max and min values, but no statistically significant difference in terms of QT disp (p < 0.001, p < 0.001, and p = 0.490). The mean (±SD) QTc max duration in the control and study groups were 439.9 ± 32.11 and 449.9 ± 37.52/ms, while QTc min was 377.8 ±30.25 and 380.7 ± 31.18/ms. There wasn’t a statistically significant difference detected between the two groups (p = 0.122 and p = 0.595). The QTc disp was measured as 54.5 in the study group and as 51.0 ms in the control group.  There wasn’t significant difference between the groups (p = 0.820). The median Tp-e max, min, and disp durations in the study and control groups were measured; 80ms-80ms, 50ms-60ms and 40ms-20ms, respectively. There was a statistically significant difference between the groups (p = 0.041, p < 0.001, and p = 0.001). The median P max, P min and P disp. were 100ms, 60ms, 40ms in the study group, and 80ms, 60ms, 20ms in the control group, respectively. There wasn’t difference in P max between the groups (p = 0.445), while there was a statistically significant difference in P min and disp p < 0.001 and p < 0.001). Results are detailed in Table 2.Cutoff values were determined by ROC analysis for P disp. and Tp-e disp, which were statistically different between groups. Area under the curve (AUC) values were 0.712 and 0.671, respectively (Figure 3). According to the highest Youden Index, the determined cutoff value was evaluated as 30 ms. According to the four-cell chart, which is based on this, sensitivity values were 87.88% and 80.3% and specificity values were 55.56% and 61.11% for P disp and Tp-e disp, respectively. The PPV, NPV, LR+, and LR− values (as measured on the website https://www.aciltipakademisi.org/istatistik-hesaplama-araclari/ by entering the data of the four-cell chart) for P disp were 70.73%, 78.95%, 1.98, and 0.22, respectively, while 71.62%, 71.74%, 2.06, and 0.32 for Tp-e disp (Table 3). Discussion: COPD is one of the leading causes of mortality and morbidity (11). Although it is seen largely in males who smoke, it is increasingly prevalence in females (12). In a systematic review and meta-analysis published in 2018 by Ntritsos et al., COPD prevalence is much higher in males than females, while the difference between the prevalence in terms of gender has been decreasing close to the age of 40 years. It was stated that, in urban areas, the prevalence was 13.03% in males and 8.34% in females, but in rural areas, it was 10.69% in males and 5.96% in females (13). When the mean age was taken into consideration, the incidence rate of COPD in males was much higher than that in females at the time the patients were included in the study (p = 0.011). A statistically significant difference wasn’t determined when the mean ages of the study and control groups were compared (p = 0.189).Electrolytes have a proarrhythmic effect by changing the cardiac ionic flow kinetics. In arrhythmia, potassium, calcium, and magnesium changes are much more effective, while sodium is less effective (14). In spite of the fact that there was a difference in K and Na electrolytes between the study and control groups in Ogan N et al. study, the mean values in the groups were within the normal reference range. When sodium and potassium values were examined, no significant difference was noted between the groups in terms of electrolytes (p = 0.353 and p = 0.071). Also, when the studies that were conducted before were compared to our study, the number of patients was found to be greater, but the mean values were similar to ours.It is known that COPD has a risk of cardiovascular disease, such as abnormality of transmission, arrhythmia, and ischemic heart disease. ECG abnormalities have been researched in patients with COPD, and it has been stated that fatal arrhythmias increase mortality in more than half of the 536STpatients (16, 17). Atrial fibrillation, multifocal atrial tachycardia, and ventricular arrhythmia are the common types in patients with COPD (18). The risk factors associated with COPD such as inhaled bronchodilators (which are the basic treatment modality), age, smoking, hypoxemia, and respiration acidosis contribute to arrhythmia (19). We evaluated the ECG parameters as a whole to predict both atrial and ventricular arrhythmias in patients with COPD. The QT duration, which is from the starting of the QRS complex to the end of the T wave, is a total duration for ventricular depolarization and repolarization. The QT duration must be straightened in regard to the heart rate to make the comparison with the reference value possible because the QT duration is affected by the heart rate (20). There was a difference between the COPD and control groups in terms of QT max and min values (p < 0.001 and p < 0.001), whereas no difference was observed in terms of QT disp (p = 0.490). There was no difference between the groups in terms of QTc max, which was straightened with regard to the heart rate, min, and disp (p = 0.122, p = 0.595, and p = 0.820). Although there was a difference between the COPD and control groups in terms of QTc disp in the study by Sarubbi et al., unlike our study, there might be a difference in the sense that the average age of the patients included in the study (62.7 ± 7.1) was younger than that in our study (68.5 [59–77]), and similarly, the average age in the control group was younger than ours (7). These ECG parameters were not used for predicting the hospitalization of patients, so these parameters are not determiners (21). In the study of Sievi et al., the average QTc of 91 patients with COPD (437.9 ± 29.5) was similar to that in our study (439.9 ± 32.11) (2). There was no difference between our control and treatment groups because the control group was at the same old age as the treatment group, and they had other chronic disorders apart from COPD.It was stated that the Tp-e duration was evaluated in different treatment groups as a sign of repolarization deformity and arrhythmia of the T wave in a review by Tse et al. Hypertension, ischemic heart disease, Brugada syndrome, Chagas disease, and pulmonary embolism took part in these treatment groups (22). Moreover, arrhythmia was tried to be seen in the treatment groups (early-stage sarcoidosis, tricyclic antidepressant intoxication, cardiac syndrome X, and acute ischemic stroke) in the literature (23–26).However, a study that predicts that the Tp-e duration foresees arrhythmia in the COPD group was not encountered in the literature. Tasolar et al. detected that the rates of Tp-e, corrected Tp-e, and Tp-e/QTc in smokers were much higher than those in nonsmokers (27). Similarly, the difference between the COPD and control groups was significant for Tp-e max, min, and disp in our study (p = 0.041, p < 0.001, and p = 0.001). In contrast, we could not detect a difference in the rate of Tp-e/QT and Tp-e/QTc differently from this study. Even if COPD stems mostly from cigarettes, it may also be seen in nonsmokers, and the patients in the control group may have other chronic disorders that would affect these consequences. The increase in the Tp-e duration is a useful parameter to foresee the events of cardiovascular disease and ventricular arrhythmia (28). In our opinion, increasing the Tp-e disp in patients with COPD contributes to the literature about predicting ventricular arrhythmia.In the study of Atar et al., P max, min, and disp were evaluated to predict arrhythmia. The COPD and control groups were compared, and no difference was found between the groups (29). We detected a significant difference between the COPD and control groups in terms of P disp. The reason for this might be that the ECG evaluation of patients during COPD attacks was not stable. In the study of Cimci et al., P wave dispersion increased in the COPD group compared to the control group (30).537STThe increases in P disp and Tp-e disp in which we detected the cutoff values in differences according to ROC analysis were 30 ms. Even though a high meaningfulness rate was not detected in the AUC and susceptibility tests, LR− values were evaluated much more meaningfully. In our opinion, our study would serve as the base for future prospective large serial studies because there is currently not enough research on this subject.Limitations: The average age of the control group in our study was similar to the treatment group, but ECG parameters might have been affected because of ignoring the chronic diseases of the patients in the control group, except COPD. Although ECG was not evaluated microscopically, required aggrandizement was done manually in a digital environment and was measured. The small number of patients involved in the study and the retrospective nature of the study are also limitations. In this study, we aimed to predict a possible arrhythmia by evaluating the ECG parameters of patients diagnosed with COPD attacks. However, we could not evaluate whether arrhythmia developed in these patients. Prospective long-term cohort studies are needed on this subject.Conclusion: To our knowledge, this is the first study that the rise of the dispersions of P wave and Tp-e intervals (without rise of QTc disp.) is detected on the evaluation of atrial and ventricular arrhythmia risks on COPD acute attacks. It is very important that a detailed ECG evaluation of these patients is performed by doctors working in the emergency service where the attack treatment is provided to diagnose early mortality, which is dependent on arrhythmia.References1. https://www.who.int/news-room/fact-sheets/detail/chronic-obstructive-pulmonary-disease-(-copd)(Date of Access 16.04.2021)2. Sievi NA, Clarenbach CF, Camen G, Rossi VA, van Gestel AJ, Kohler M. High prevalence of altered cardiac repolarization in patients with COPD. BMC Pulm Med. 2014 Apr 2;14:55. doi: 10.1186/1471-2466-14-55. PMID: 24690123; PMCID: PMC3976227.3. Straus SM, Kors JA, De Bruin ML, van der Hooft CS, Hofman A, Heeringa J, et al. Prolonged QTc interval and risk of sudden cardiac death in a population of older adults. J Am Coll Cardiol. 2006 Jan 17;47(2):362-7. doi: 10.1016/j.jacc.2005.08.067. PMID: 16412861.4. Larssen MS, Steine K, Hilde JM, Skjørten I, Hodnesdal C, Liestøl K, et al. Mechanisms of ECG signs in chronic obstructive pulmonary disease. Open Heart. 2017 Mar 22;4(1):e000552. doi: 10.1136/openhrt-2016-000552. PMID: 28533915; PMCID: PMC5437720.5. Fuso L, Incalzi RA, Pistelli R, Muzzolon R, Valente S, Pagliari G, et al. Predicting mortality of patients hospitalized for acutely exacerbated chronic obstructive pulmonary disease. Am J Med. 1995 Mar;98(3):272-7. doi: 10.1016/s0002-9343(99)80374-x. PMID: 7872344.6. Hudson LD, Kurt TL, Petty TL, Genton E. Arrhythmias associated with acute respiratory failure in patients with chronic airway obstruction. Chest. 1973 May;63(5):661-5. doi: 10.1378/chest.63.5.661. PMID: 4122207.7. Sarubbi B, Esposito V, Ducceschi V, Meoli I, Grella E, Santangelo L, et al. Effect of blood gas derangement on QTc dispersion in severe chronic obstructive pulmonary disease: evidence of an electropathy? Int J Cardiol. 1997 Feb;58(3):287-92. doi: 10.1016/s0167-5273(96)02876-8. PMID: 538ST9076557.8. Kiely DG, Cargill RI, Lipworth BJ. Effects of hypercapnia on hemodynamic, inotropic, lusitropic, and electrophysiologic indices in humans. Chest. 1996 May;109(5):1215-21. doi: 10.1378/chest.109.5.1215. PMID: 8625670.9. Goudis CA, Konstantinidis AK, Ntalas IV, Korantzopoulos P. Electrocardiographic abnormalities and cardiac arrhythmias in chronic obstructive pulmonary disease. Int J Cardiol. 2015 Nov 15;199:264-73. doi: 10.1016/j.ijcard.2015.06.096. Epub 2015 Jul 4. PMID: 26218181.10. Rosenthal TM, Masvidal D, Abi Samra FM, Bernard ML, Khatib S, Polin GM, et al. Optimal method of measuring the T-peak to T-end interval for risk stratification in primary prevention. Europace. 2018 Apr 1;20(4):698-705. doi: 10.1093/europace/euw430. PMID: 28339886.11. Adeloye D, Chua S, Lee C, Basquill C, Papana A, Theodoratou E, et al. Global and regional estimates of COPD prevalence: Systematic review and meta-analysis. J Glob Health. 2015 Dec;5(2):020415. doi: 10.7189/jogh.05-020415. PMID: 26755942; PMCID: PMC4693508.12. Aryal S, Diaz-Guzman E, Mannino DM. Influence of sex on chronic obstructive pulmonary disease risk and treatment outcomes. Int J Chron Obstruct Pulmon Dis. 2014 Oct 14;9:1145-54. doi: 10.2147/COPD.S54476. PMID: 25342899; PMCID: PMC4206206.13. Ntritsos G, Franek J, Belbasis L, Christou MA, Markozannes G, Altman P, et al. Gender-specific estimates of COPD prevalence: a systematic review and meta-analysis. Int J Chron Obstruct Pulmon Dis. 2018 May 10;13:1507-1514. doi: 10.2147/COPD.S146390. PMID: 29785100; PMCID: PMC5953270.14. El-Sherif N, Turitto G. Electrolyte disorders and arrhythmogenesis. Cardiol J. 2011;18(3):233-45. PMID: 21660912.15. Ogan N, Günay E, Baha A, Çandar T, Akpınar EE. The Effect of Serum Electrolyte Disturbances and Uric Acid Level on the Mortality of Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease. Turk Thorac J. 2020 Sep;21(5):322-328. doi: 10.5152/TurkThoracJ.2019.19034. Epub 2020 Sep 1. PMID: 33031723; PMCID: PMC7544412.16. Bhatt SP, Dransfield MT. Chronic obstructive pulmonary disease and cardiovascular disease. Transl Res. 2013 Oct;162(4):237-51. doi: 10.1016/j.trsl.2013.05.001. Epub 2013 May 31. PMID: 23727296.17. Zaghla AH, Atroush HA, Samir A, Kamal M. Arrhythmias in patients with chronic obstructive pulmonary disease. Egypt. J. ChestDis. Tuberc. 62 (2013) 377–385.18. Sode BF, Dahl M, Nordestgaard BG. Myocardial infarction and other co-morbidities in patients with chronic obstructive pulmonary disease: a Danish nationwide study of 7.4 million individuals. Eur Heart J. 2011 Oct;32(19):2365-75. doi: 10.1093/eurheartj/ehr338. Epub 2011 Aug 29. PMID: 21875856.19. Górecka D. Cardiac arrhythmias in chronic obstructive pulmonary disease. Monaldi Arch Chest Dis. 1997 Jun;52(3):278-81. PMID: 9270257.20. Postema PG, Wilde AA. The measurement of the QT interval. Curr Cardiol Rev. 2014 Aug;10(3):287-94. doi: 10.2174/1573403x10666140514103612. PMID: 24827793; PMCID: PMC4040880.539ST21. Dogan NO, Pekdemir M, Yilmaz S, Yaka E, Avcu N, Durmus U, et al. Role of Electrocardiographic Manifestations in Admission Decision in Patients with Chronic Obstructive Pulmonary Disease Exacerbation. J Coll Physicians Surg Pak. 2019 Feb;29(2):109-114. doi: 10.29271/jcpsp.2019.02.109. PMID: 30700346.22. Tse G, Gong M, Wong WT, Georgopoulos S, Letsas KP, Vassiliou VS, et al. The Tpeak - Tend interval as an electrocardiographic risk marker of arrhythmic and mortality outcomes: A systematic review and meta-analysis. Heart Rhythm. 2017 Aug;14(8):1131-1137. doi: 10.1016/j.hrthm.2017.05.031. Epub 2017 May 26. PMID: 28552749.23. Kasapkara HA, Şentürk A, Bilen E, Ayhan H,

MTHFR Eksikliği Tanısı ile Takip Edilen Hastaların Klinik, Laboratuvar ve Moleküler Bulgularının Değerlendirilmesi

MTHFR Eksikliği Tanısı ile Takip Edilen Hastaların Klinik, Laboratuvar ve Moleküler Bulgularının DeğerlendirilmesiÖzge Kamer Karalar Pekuz1, Pelin Teke Kısa1, Esra Er2, Sedef Sezen3, Sevil Dorum4, Zümrüt Arslan Gülten5, Banu Kadıoğlu Yılmaz6, Özlem Ünal Uzun7, Halil İbrahim Aydın8, Mustafa Kılıç9, Bahar Kulu1 Şahin Erdöl3, Nur Arslan11Dokuz Eylül Üniversitesi Tıp Fakültesi Çocuk Sağlığı ve Hastalıkları AD, Çocuk Metabolizma Hastalıkları Bilim Dalı, İzmir2 S.B.Ü. Dr.&nbsp;Behçet Uz&nbsp;Çocuk Hastalıkları Ve Cerrahisi Eğitim Ve Araştırma Hastanesi Çocuk Sağlığı ve Hastalıkları AD, Çocuk Metabolizma Hastalıkları Bilim Dalı, İzmir3Uludağ Üniversitesi Tıp Fakültesi, Çocuk Sağlığı ve Hastalıkları AD, Çocuk Metabolizma Hastalıkları Bilim Dalı, Bursa4 S.B.Ü.&nbsp;Bursa Yüksek İhtisas&nbsp;E.A.H, Çocuk Sağlığı ve Hastalıkları AD, Çocuk Metabolizma Hastalıkları Bilim Dalı, Bursa5 S.B.Ü.&nbsp;Şişli Hamidiye Etfal&nbsp;Eğitim ve Araştırma&nbsp;Hastanesi, Çocuk Sağlığı ve Hastalıkları AD, Çocuk Metabolizma Hastalıkları Bilim Dalı, İstanbul6&nbsp;&nbsp; Selçuk Üniversitesi Tıp Fakültesi Hastanesi Çocuk Sağlığı ve Hastalıkları AD, Çocuk Metabolizma Hastalıkları Bilim Dalı, Konya7 Kocaeli Üniversitesi Tıp Fakültesi Çocuk Sağlığı ve Hastalıkları AD, Çocuk Metabolizma Hastalıkları Bilim Dalı, Kocaeli8 Başkent Üniversitesi Ankara Hastanesi Çocuk Sağlığı ve Hastalıkları AD, Çocuk Metabolizma Hastalıkları Bilim Dalı, Ankara9Ankara Etlik Şehir Hastanesi,Çocuk Sağlığı ve Hastalıkları AD, Çocuk Metabolizma Hastalıkları Bilim Dalı, Ankara&nbsp;Giriş ve amaç: Metilentetrahidrofolat redüktaz (MTHFR) eksikliği [MIM 607093; MTHFR; 1p36.22], otozomal resesif geçişli, nadir görülen kalıtsal metabolik hastalıktır. MTHFR enziminin eksikliği, metiyonin sentezine katılan 5- Metilentetrahidrofolatın eksikliğine yol açar. Yetersiz remetilasyon, kanda homosisteinin ciddi şekilde yükselmesine ve metiyonin konsantrasyonunun azalmasına yol açar. Yüksek homosistein ve düşük metiyonin tromboembolik olaylar ve nörogelişimsel bozukluklarla ilişkilidir. MTHFR eksikliği farklı yaşlarda bugu verebilir, klinik heterojendir, çeşitli nörolojik bulgular ile prezente olabilir.&nbsp; Nörolojik bulgular temel olarak S-adenosilmetiyonin serebral eksikliği nedeniyle oluşan kusurlu miyelinizasyona bağlanmaktadır. Ağır MTHFR eksikliği olan hastalarda klinik tipik olarak yenidoğan döneminde beslenme sorunları, gelişme geriliği, &nbsp;hipotoni, mikrosefali, ensefalopati ve nöbetlerle ortaya çıkar. Apne sık görülen bir komplikasyondur. Ancak geç başlangıçlı hastalıkta, gelişimsel gecikme, bilişsel bozukluklar ve/veya yürüyüş anormallikleri, periferik nöropati, spastisite, psikiyatrik bozukluklar veya tromboembolik olayları kapsayan daha değişken bir tablo görülebilir. Tedavi edilmediğinde morbiditesi ve mortalitesi yüksek bir hastalıktır. Betain tedavisi ile nörolojik bulgularda stabilizasyon sağlandığı gösterilmiştir. Ek olarak, hastalara folinik asit, l-karnitin ve metiyonin tedavileri başlanabilir. Protein kısıtlamasından, folik asit tedavisinden ve nitröz oksit maruziyetinden kaçınılmalıdır. Ülkemizde MTHFR eksikliğinin klinik bulguları ile ilgili kapsamlı bir çalışma bulunmamaktadır. Bu çalışmanın amacı nadir görülen bir hastalık olan&nbsp; MTHFR eksikliği hastalarının klinik bulgularını ortaya koymak,&nbsp; laboratuvar bulguları ve moleküler sonuçlarını dökümante etmektir.Gereç ve yöntem: Klinik ve biyokimyasal olarak MTHFR eksikliği tanısı ile takip edilen 15 hasta retrospektif olarak dosya kayıtları incelendi. Demografik veriler, başvuru ve tanı yaşı, başvuru şikâyeti, nörolojik bulgular, ek klinik bulgular, tanı anındaki laboratuvar bulgular, görüntüleme sonuçları ve moleküler analiz sonuçları, kullanmakta oldukları tedaviler veri formuna kayıt edildi.Bulgular: Olguların 6’sı kız, 9’u erkek, yaş ortanca 70 ay (min -maks: 2 -300 ay), tanı yaşı ortanca 10 ay (min -maks : 1-168 ay) saptandı. 12 hastada (%80) akrabalık mevcuttu. Olguların semptom başlangıç yaşı ortanca 4 ay (min-maks :0.33-144 ay), ilk başvuru yaşı ortanca 6 ay (min- maks: 0.33- 276 ay) olarak bulundu. Hastaların ilk semptomları beslenememe, hipotoni, nöbet, nöromotor gelişim geriliği olarak saptandı. Bu bulgular 9 hastada yenidoğan döneminde başlamıştı. Mikrosefali olguların 9’unda (%60) saptandı. 10 hastada nöbet öyküsü saptandı.&nbsp; Tüm hastaların tanı anındaki homosistein değerleri &gt;50 mmol/L idi. Metiyonin değerleri ortalaması 8.1± 4.9 mmol/L saptandı. Tüm hastaların idrar organik asit analizinde metil malonik asit atılımı normaldi. Tüm hastalar betain tedavisi almaktaydı. Medyan takip süresi 45 ay (min- maks: 4- 288 ay) bulundu. İki hasta sepsis ve solunum yetmezliği nedeni ile kaybedilmişti. Hastalara ait demografik, klinik &nbsp;ve moleküler bulgular Tablo-1’ de özetlenmiştir.Tartışma: Yenidoğan tarama programı kapsamında homosistein düzeyi içeren ülkelerde yapılan çalışmalar sonucunda MTHFR eksikliğinde erken tanı ve tedavi ile morbidite ve mortalitede azalma olduğu gösterilmiştir. Güncel literatürler ile karşılaştırıldığında, çalışmamızda tanı yaşı ileri bulundu. Özellikle yenidoğan döneminde bulgu veren ağır MTHFR eksikliği olan hastalarda tedavi geciktiğinde ciddi nörolojik tutulum ile sonuçlanmaktadır. Betain tedavisinin metionin düzeylerini normalleştirdiği ve homosistein düzeylerini azalttığı, semptomatik hastalarda bilişsel gerilemeyi önleyebileceği ve ölüm riskini azalttığı gösterilmiştir. Ülkemizde henüz yenidoğan tarama programında bulunmamaktadır. Sonuç olarak; MTHFR eksikliği esas olarak santral sinir sistemi bulguları ile prezente olan bir kalıtsal metabolik hastalıkltır. Bu nedenle nörolojik bulgular ile başvuran tüm hastalarda homosistein düzeyi bakılmalı ve yüksek homosisten düzeyi saptandığında betain tedavisi ivedilikle başlanmalıdır.&nbsp;&nbsp;Anahtar kelimeler: Homosistein, betain, MTHFR eksikliği, epilepsi, mikrosefali, hipotoni,Kaynaklar:1) Huemer M, Diodato D, Schwahn B, et al. Guidelines for diagnosis and management of the cobalamin-related remethylation disorders cblC, cblD, cblE, cblF, cblG, cblJ and MTHFR deficiency.&nbsp;J Inherit Metab Dis. 2017;40(1):21-48. doi:10.1007/s10545-016-9991-42) Huemer M, Mulder-Bleile R, Burda P, et al. Clinical pattern, mutations and in vitro residual activity in 33 patients with severe 5, 10 methylenetetrahydrofolate reductase (MTHFR) deficiency.&nbsp;J Inherit Metab Dis. 2016;39(1):115-124. doi:10.1007/s10545-015-9860-63) Strauss KA, Morton DH, Puffenberger EG, et al. Prevention of brain disease from severe 5,10-methylenetetrahydrofolate reductase deficiency.&nbsp;Mol Genet Metab. 2007;91(2):165-175. doi:10.1016/j.ymgme.2007.02.0124) Huemer M, Diodato D, Martinelli D, et al. Phenotype, treatment practice and outcome in the cobalamin-dependent remethylation disorders and MTHFR deficiency: Data from the E-HOD registry.&nbsp;J Inherit Metab Dis. 2019;42(2):333-352. doi:10.1002/jimd.12041&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;<span style="font-size: 10pt; line-height: 20