Vitamin E Level In Friedreich ’ s Ataxic Phenotype Patients In Four Major Hospitals In Baghdad

Al-Kindy College Medical Journal 2017: Vol.13 No. 1 132 www.kmjub.com ABSTRACT Background: Friedreich ataxia (FRDA) is the most common form of inherited ataxia, comprising one-half of all hereditary ataxias with a carrier rate between 1 in 60 to 1 in 90 and with a disease prevalence of 1 per 29,000. It can occur in two forms the classic form or in association with a vitamin E dependent ataxia. The precise role of Vitamin E in the nervous system is unknown; An Oxidative attack is suspected to play a role in Ataxia with Vitamin E deficiency, as well as in Friedreich ataxia. Vitamin E is the major freeradical-trapping antioxidant. Objective: The objectives of the study is to asses vitamin E level in patients with Friedreichs ataxia phenotype in Iraqi patients. Type of the study:Cross-sectional study. Method: This study was conducted at the neuroscience hospital and Baghdad teaching hospital during the period from the 1st of November 2013 through November 2014. Forty patients with friedreich's ataxia attended in neuroscience hospital and Baghdad teaching hospital during this period; there was12 male, 20 female patients and their age range between (4-50) years. Results: Regarding the level of vitamin E in patients in the present study, The study revealed that mean level of vitamin E for Friedreich ataxia patients was (10.92 μg/ml) ranging from (8-18 μg/ml),while in the control group the mean was (28.06μg/ml) ranging from (22-36μg/ml), the difference in mean level was found to be statistically significant (p=0.0001.) Thirty percents of (FRDA) patients was (89.9μg/ml), while half of patients (50%) were within (10-11.9 μg/ml),and low percentage (15 %)of patients were within (12-13.9 μg/ml ). The rest (5%) were had vitamin E level equal or more than 14 μg/ml. these finding revealed that majority of Friedreich ataxia patients were found with low level of vitamin E (32 patients(80%)), and low percentage with normal level (8 patients(20%.)) Patients with Friedreich ataxia were found to have a comparable level 10.47±1.79(8.4-13.5),11.48±2.61(9.4-18) and 10.66±1.26(912.5) for those with less than 10 years, 10-19 years , equal or more than 20 years of age respectively (p=0.382), while it was found to have a significantly decreasing level with advance in the age for the control group, 30.57±4.61(24.536), 27.46±3.16(23.7-33.5), 25.50±3.03 (22.9-29) for those less than 10 years, 10-19 years, 20 years or more respectively (p=0.006.) Vitamin E level in relation to Gender showed that Friedriech ataxia male patients had significantly higher vitamin E level compared to females [12.05±2.66 (9.0-18.0) compared to 10.17±1.07 (8.4-12.0)] (p=0.003), while relation to gender in the control group was not of significant value statistically [27.08±2.90 (22.9-30.0) for male compared to 29.04±4.97 (23.7-36) for females] , p=0.136. Conclusion: In the light of the results of the present study, the following conclusions were made: The level of vitamin E in friedreichs ataxic phenotype patients was subnormal than normal range representing 80% of the sample selected for the test. The level of vitamin E in male patients of freidriechs ataxic phenotype patients was higher than female patients.

riedreich ataxia (FRDA) is the most common form of inherited ataxia, and is the most common form of the autosomal recessive ataxias comprising one-half of all hereditary ataxias1.It can occur in two forms the classic form or in association with a vitamin E dependent ataxia.Clinical features include progressive limb and gait ataxia, dysarthria, loss of joint position and vibration senses, absent tendon reflexes in the legs, and extensor plantar responses2.The onset of Friedreich ataxia is early; it typically presents in children aged (8-15 years) and almost always presents before age 20 year, Friedreich ataxia is a relatively common disorder.Overall, the Friedreich ataxia carrier rate has been estimated recently to be 1 in 60 to 1 in 90, with a disease prevalence of 1 per 29,000.Loss of ambulation typically occurs 15 years after disease onset.More than 95% of patients are wheelchair bound by age 45 years.
The average age of age of death was 37.7 years, the most common cause of death in Friedreich ataxia patients is the cardiac failure and arrhythmia.Classic Friedreich ataxia is the result of a gene mutation at the centromeric region of chromosome 9 (9q13-21.1)at the site of the gene encoding for the frataxin (210-aminoacid protein).In a normal chromosome, this trinucleotide sequence is repeated up to 50 times.In patients with FA, this sequence is repeated at least 200 times and often more than 1000 times, Variability in the clinical presentation of Friedreich ataxia may be explained by the extent of this trinucleotide expansion .Ataxia with Vitamin E deficiency (AVED), is inherited with an autosomal recessive pattern, The abnormal gene was mapped to chromosome 8q and identified as the gene encoding for α-tocopherol transfer protein (α-TTP) (3,4,5,6,7,8) (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) years, (20 male-20 female) recruited from hospital staff and their relatives to test for the level of vitamin E .Examination of patients and control done by specialist neurologist in Baghdad teaching hospital and neuroscience hospital, each patients send for vitamin E assessment at the same lab according to shape below (see session 2.3),all the patients had previous MRI and were revised by researcher.Serum concentration of vitamin E are measured using high performance liquid chromatography (HPLC) with photodiode array detection, small volume (100 ml) butyrate, the micronutrients are extracted from the aqueous phase into hexane and dried under vacuum .theextract is dissolved in ethanol and acetonitrile and is filtered to remove an insoluble material.An aliquot of the filtrate is injected onto a c18 reversed phase column and isocratic ally eluted with a mobile phase consisting of equal parts of ethanol and acetonitrile.Absorbance of these substantices in solution is linearly proportional to concentration (within limits), thus spectro photo metric methods are used for quantitative analysis.Three wavelength approximately corresponding to absorption maxima 300,325,450 nm, are simultaneously monitored achrmota grams are recorded.Quantitation is accomplished by comparing the peak height or area of analyte in the unknown with peak height or area of unknown amount of same analyte in acaliber solution.Calculations are corrected based on the peak height or area of the internal standard in the unknown compared with the peak height or area of internal standard in acaliber solution.Retinol   This table  shows that vitamin e level in (30% ) of (FRDA) patients was (8-9.9µg/ml),(50%) were with (10-11.9µg/ml), (15 %) were of (12-13.9µg/ml ), and (5%) were with vitamin E level of equal or more than 14 µg/ml.
These finding revealed that majority of Friedreich ataxia patients were found with low vitamin E (32 patients; 80%), and low percentage with normal level (8 patients; 20%).
Table (3)(4)The level of vitamin E for the (FRDA) and control according to age and gender.

Figure (3-1
) the level of vitamin E for the (FRDA) and control according to age and gender.
The results in the table 3.4 showed that level of vitamin E were (10.47±1.79),(11.48±2.61)and (10.66±1.26) in patients less than 10 years , patients between 10-19 years, and for those equal or more than 20 years of age respectively, (p=0.382),See the table (3)(4).The level of vitamin E in control patients were ( 30.57±4.61),(27.46±3.16) and(25.50±3.03)for patients less than 10 years age, patients between 10-19 years, and for those equal or 20 years or more respectively and it was statically significant, (p=0.006),see the table (3)(4).The level of vitamin E in friedreichs ataxic phenotypic patients according to the Gender showed that male patients had higher vitamin E level (12.05±2.66)compared to females(10.17±1.07)and it was statically significant(p=0.003),see the table (3)(4).The level of vitamin E in relation to the gender in the control group showed that female patients were (29.04±4.97),whereas male patients were(22.9-30.0),the result was not statistically significant(p=0.136),see the table (3)(4).
Discussion: Friedeichs ataxia is a relatively common disorder with significant morbidity associated with a range of deleterious consequences, including higher morbidity, restriction on social activities, and stress on the patient's family members and caregivers.It is also a great economic burden for the society through expenditures in healthcare and unemployment.The patients age range with Friedreich ataxia phenotype in this study who were of (

F*
Significant difference between proportions using Pearson Chi-square test at 0.05.
n ± S D ( R a n g e ) # S i g n i f i c a n t d i f f e r e n c e b e t w e e n t h r e e i n d e p e n d e n t m e a n s u s i n g A N O V A t e s t a t 0 .0 5 .* S i g n i f i c a n t d i f f e r e n c e b e t w e e n t w o i n d e p e n d e n t m e a n s u s i n g S t u d e n t -t -t e s t a t 0 .0 5 .
. It is difficult to distinguish on the basis of F Vitamin E Level ….Ahmed Hasan Ahmed et al Al-Kindy College Medical Journal 2017: Vol.13 No. 1 133 www.kmjub.com (10)e was also difficulty in delivering sample of blood to the lab in appropriate time, that makes false positive result because of sensitivity to the hot environment, and the time to take the sample to the lab since the lab is away from the patients.It's a hospital-based study and its results may not reflect the real picture in the general population.Another limitation was that most of friedreichs ataxic phenotype patient attend the private clinic and not attending the hospital that lead to low number of patients in this study.Conclusion:In the light of the results of the present study, the following conclusions were made:1-The level of vitamin E in friedreichs ataxic phenotype patients was subnormal than normal range representing 80% of the sample selected for the test.2-Thelevel of vitamin E in male patients of freidriechs ataxic phenotype patients was higher than female patients.www.kmjub.com17.Cooper JM, Korlipara LV, Hart PE, Bradley JL, Schapira AH et (2008) Coenzyme Q(10)and vitamin E deficiency in Friedreich's ataxia: predictor of efficacy of vitamin E and coenzyme Q(10) therapy.Eur J Neurol ,