Amaç: Bu çalışmada farklı tiplerinde değişen oranlarda multisistemik tutuluma, nörolojik bulguların da eşlik ettiği mukopolisakkaridozlu hastalarda, serum vitamin B12 düzeylerinin de klinik seyir üzerine etkisi araştırılmıştır. Gereç ve Yöntem: Bu çalışmaya enzim düzeyi ve mutasyon analizi ile mukopolisakkaridoz tanısı konulan 114 hasta çalışmaya dahil edildi. Bu hastalardan periyodik takipleri sırasında sistemik ve nörolojik değerlendirmeye ek olarak serum vitamin B12 düzeyleri ölçüldü. Vitamin B12 düzeyi <300 pg/ml eksiklik olarak kabul edildi. Bulgular: Ortalama serum vitaminB12 seviyeleri 399,4 ± 258,5 pg/mL idi. Hastaların 53’ünde (%46,5) serum B12 seviyesi 300 pg/ml'nin altındaydı. Mukopolisakkaridozlu çocuklarda serum B12 vitamini düzeyi, literatürdeki sağlıklı çocuklardan önemli ölçüde düşüktü. Erkeklerde vitamini B12 eksikliği kızlara göre istatistiksel olarak anlamlı derecede fazlaydı. Tipler arası değerlendirmede MPS tip II tanılı hastalarda vitamin B12 düzeyindeki düşüklüğün anlamlı olarak diğer alt gruplardan daha yüksek olduğu görüldü. Sonuç: Mukopolisakkaridozlu hastalarda etiyopatogenezi net olmamakla birlikte, vitamin B12 seviyesi sağlıklı ve kronik hastalığı olan diğer bireylerden daha düşük bulunmuştur. Vitamin B12 eksikliği hastalığın doğal seyrinde ki büyüme geriliği ve nöromotor fonksiyon etkilenmesini daha da arttıracağı için, çalışmamız sonucunda mukopolisakkaridozlu hastalarda vitamin B12 düzeyinin de rutin monitorizasyonunun gerekliliği ortaya konulmuştur.
1. Tomatsu S, Pitz S, Hampel U. Ophthalmological Findings in Mucopolysaccharidoses. J. Clin. Med 2019;8(9):1467. doi:10.3390/jcm8091467.
2. Venkatramanan S, Armata IE, Strupp BJ, Finkelstein JL. Vitamin B-12 and Cognition in Children. American Society for Nutrition. Adv Nutr 2016;7:879–88. doi:10.3945/an.115.012021.
3. Solomon LR. Cobalamin-responsive disorders in the ambulatory care setting: unreliability of cobalamin, methylmalonic acid, and homocysteine testing. Blood 2005;105(3):978-85.
4. Yetim A, Aygün E, Yetim Ç, Ucar A, Karakaş Z¸ Gökçay G, Demirkol M. Measurement of serum vitamin B12-related metabolites in newborns: implications for new cutoff values to detect B12 deficiency. J Matern Fetal Neonatal Med 2019;2:1-9. doi: 10.1080/14767058.2019.1633301.
5. Carmel R. Current concepts in cobalamin deficiency. Annu Rev Med 2000;51:357–75.
6. Miranti EH, Stolzenberg-Solomon R, Weinstein SJ, Selhub J, Männistö S, Taylor PR et al. Low vitamin B12 increases risk of gastric cancer: a prospective study of onecarbon metabolism nutrients and risk of upper gastrointestinal tract cancer. Int J Cancer 2017;141:1120–9.
7. Pan YL, Liu Y, Guo H, Jabir MS, Liu X, Cui W et al. Associations between folate and vitamin B12 levels and inflammatory bowel disease: a meta-analysis. Nutrients 2017;9(4):382.
8. Thomson ABR, Sauve MD, Kassam N, Kamitakahara H. Safety of the long-term use of proton pump inhibitors. World J Gastroenterol. 2010;16(19):2323–30.
9. Pierce SA, Chung AH, Black KK. Evaluation of vitamin B12 monitoring in a veteran population on long-term, high-dose metformin therapy. Ann Pharmacother 2012;46(11):1470-6.
10. Goraya JS, Kaur S, Mehra B. Neurology of nutritional vitamin B12 deficiency in infants: case series from India and literature review. J Child Neurol 2015;30:1831-7.
11. de Benoist B. Conclusions of a WHO Technical Consultation on folateand vitamin B12 deficiencies. Food Nutr Bull 2008;29(2):238-44.
12. Green R, Allen L, Bjørke-Monsen A, Brito A, Guéant JL, Miller JW et al. Vitamin B12 deficiency. Nat Rev Dis Prim 2017;3: 17040.
13. Şahin Erdöl. Önemli Bir Halk Sağlığı Problemi: Vitamin B12 Eksikliği. Güncel pediatri 2017;15(2):30-3.
14. Onal H, Adal E, Oner T, Onal Z, Aydın A. An important problem in developing countries: maternal and neonatal vitamin B12 deficiency. Turk Arc Ped 2010;45:242-5.
15. Koc A, Kocyigit A, Soran M, Demir N, Sevinc E, Erel O, et al. High frequency of maternal vitamin B12 deficiency as an important cause of infantile vitamin B12 deficiency in Şanlıurfa province of Turkey. Eur J Nurt 2006;45:291-7.
16. Wetherilt H, Ackurt F, Brubacher G, Okan B, Aktas S, Turdu S. Blood vitamin and mineral levels in 7-17 years old Turkish children. Int J Vitam Nutr Res. 1992;62(1):21-9.
17. Öncel K, Özbek MN, Onur H, Söker M, Ceylan A. Diyarbakır İlindeki Çocuklarda ve Adölesanlarda B12 Vitamin ve Folik Asit Düzeyleri. Dicle Tıp Dergisi 2006;33(3):163-9.
18. Koç A, Koçyiğit A, Ulukanlıgil M, Demir N. Şanlıurfa yöresinde 9-12 yaş grubu çocuklarda B12 vitamini ve folik asit eksikliği sıklığı ile bağırsak solucanlarıyla ilişkisi. Çocuk Sağlığı ve Hastalıkları Dergisi 2005;48:308-15.
19. Calik M, Aktas MS, Cecen E, Piskin IE, Ayaydın H, Ornek Z et al. The association between serum vitamin B12 deficiency and tension-type headache in Turkish children. Neurol Sci 2018;39(6):1009-14. doi: 10.1007/s10072-018-3286-5.
20. Altun H, Şahin N, Belge Kurutaş E, Güngör O. Homocysteine, Pyridoxine, Folate and Vitamin B12 Levels in Children with Attention Deficit Hyperactivity Disorder. Psychiatr Danub, 2018;30(3):310-6.
21. Meena MK, Sharma S, Bhasin H, Jain P, Kapoor S, Jain A et al. Vitamin B12 Deficiency in Children With Infantile Spasms: A Case-Control Study. Journal of Child Neurology 2018;33(12):767-71.
22. Ho M, Halim JH, Gow ML, El-Haddad N, Marzulli T, Baur LA et al. Vitamin B12 in Obese Adolescents with Clinical Features of Insulin Resistance. Nutrients 2014;6(12):5611-8. doi:10.3390/nu6125611.
23. Emen B, Kılıç Öztürk Y, Eren MA, Özdemir E, Öztürk F, Düzenli E et al. B12 Vitamin Eksikliği Bulunan Hastalarda Etiyolojik Faktörler İle Laboratuvar Verileri Arasındaki İlişkinin Geriye Dönük Değerlendirilmesi. Tepecik Eğit Hast Derg 2013;23(1):19-23.
24. VanderJagt DJ, Spelman K, Ambe J, Datta P, Blackwell W, Crossey M et. al. Folate and vitamin B12 status of adolescent girls in northern Nigeria. J Nat Med Assoc 2000;92:334-40.
25. Osifo BO, Lukanmbi FA, Bolodeoku JO. Reference values for serum folate, erythrocyte folate and serum cobalamin in Nigerian adolescents. Trop Geogr Med 1986;38:259-64.
26. Margalit I, Cohen E, Goldberg E, Krause I. Vitamin B12 Deficiency and the Role of Gender: A Cross-Sectional Study of a Large Cohort. Ann Nutr Metab 2018;72:265–71.
Vitamin B12 levels in patients with mucopolysaccharidosis
Year 2020,
Volume: 45 Issue: 2, 401 - 407, 30.06.2020
Purpose: The aim of this study was to investigate the relationship between serum vitamin B12 levels and clinical course of mucopolysaccharidosis patients with different subtypes and variable multisystemic involvement including neurological manifestations. Materials and Methods: 114 mucopolysaccharidosis patients diagnosed by enzymatic or molecular analysis were included in the study. In addition to systemic and neurological assessments, vitamin B12 levels were measured periodically. Vitamin B12 level below 300 pg/ml was defined as deficiency. Results: Serum B12 levels of 53 patients were below 300 pg/ml. Serum B12 levels of patients with mucopolysaccharidosis were significantly low compared to healthy children reported in the literature. Vitamin B12 deficiency was significantly prevalent in males compared to females. Evaluation of prevalence of vitamin B12 deficiency between subtypes indicated vitamin B12 deficiency was significantly prevalent in mucopolysaccharidosis type II. Conclusion: Although the exact etiopathogenesis is not completely understood, vitamin B12 levels were lower than healthy children or children with different chronic diseases. Since vitamin B12 deficiency may intensify the growth retardation and neuromotor deficit due to the natural course of mucopolysaccharidosis, our study revealed the necessity of routine monitorization of vitamin B12 levels.
1. Tomatsu S, Pitz S, Hampel U. Ophthalmological Findings in Mucopolysaccharidoses. J. Clin. Med 2019;8(9):1467. doi:10.3390/jcm8091467.
2. Venkatramanan S, Armata IE, Strupp BJ, Finkelstein JL. Vitamin B-12 and Cognition in Children. American Society for Nutrition. Adv Nutr 2016;7:879–88. doi:10.3945/an.115.012021.
3. Solomon LR. Cobalamin-responsive disorders in the ambulatory care setting: unreliability of cobalamin, methylmalonic acid, and homocysteine testing. Blood 2005;105(3):978-85.
4. Yetim A, Aygün E, Yetim Ç, Ucar A, Karakaş Z¸ Gökçay G, Demirkol M. Measurement of serum vitamin B12-related metabolites in newborns: implications for new cutoff values to detect B12 deficiency. J Matern Fetal Neonatal Med 2019;2:1-9. doi: 10.1080/14767058.2019.1633301.
5. Carmel R. Current concepts in cobalamin deficiency. Annu Rev Med 2000;51:357–75.
6. Miranti EH, Stolzenberg-Solomon R, Weinstein SJ, Selhub J, Männistö S, Taylor PR et al. Low vitamin B12 increases risk of gastric cancer: a prospective study of onecarbon metabolism nutrients and risk of upper gastrointestinal tract cancer. Int J Cancer 2017;141:1120–9.
7. Pan YL, Liu Y, Guo H, Jabir MS, Liu X, Cui W et al. Associations between folate and vitamin B12 levels and inflammatory bowel disease: a meta-analysis. Nutrients 2017;9(4):382.
8. Thomson ABR, Sauve MD, Kassam N, Kamitakahara H. Safety of the long-term use of proton pump inhibitors. World J Gastroenterol. 2010;16(19):2323–30.
9. Pierce SA, Chung AH, Black KK. Evaluation of vitamin B12 monitoring in a veteran population on long-term, high-dose metformin therapy. Ann Pharmacother 2012;46(11):1470-6.
10. Goraya JS, Kaur S, Mehra B. Neurology of nutritional vitamin B12 deficiency in infants: case series from India and literature review. J Child Neurol 2015;30:1831-7.
11. de Benoist B. Conclusions of a WHO Technical Consultation on folateand vitamin B12 deficiencies. Food Nutr Bull 2008;29(2):238-44.
12. Green R, Allen L, Bjørke-Monsen A, Brito A, Guéant JL, Miller JW et al. Vitamin B12 deficiency. Nat Rev Dis Prim 2017;3: 17040.
13. Şahin Erdöl. Önemli Bir Halk Sağlığı Problemi: Vitamin B12 Eksikliği. Güncel pediatri 2017;15(2):30-3.
14. Onal H, Adal E, Oner T, Onal Z, Aydın A. An important problem in developing countries: maternal and neonatal vitamin B12 deficiency. Turk Arc Ped 2010;45:242-5.
15. Koc A, Kocyigit A, Soran M, Demir N, Sevinc E, Erel O, et al. High frequency of maternal vitamin B12 deficiency as an important cause of infantile vitamin B12 deficiency in Şanlıurfa province of Turkey. Eur J Nurt 2006;45:291-7.
16. Wetherilt H, Ackurt F, Brubacher G, Okan B, Aktas S, Turdu S. Blood vitamin and mineral levels in 7-17 years old Turkish children. Int J Vitam Nutr Res. 1992;62(1):21-9.
17. Öncel K, Özbek MN, Onur H, Söker M, Ceylan A. Diyarbakır İlindeki Çocuklarda ve Adölesanlarda B12 Vitamin ve Folik Asit Düzeyleri. Dicle Tıp Dergisi 2006;33(3):163-9.
18. Koç A, Koçyiğit A, Ulukanlıgil M, Demir N. Şanlıurfa yöresinde 9-12 yaş grubu çocuklarda B12 vitamini ve folik asit eksikliği sıklığı ile bağırsak solucanlarıyla ilişkisi. Çocuk Sağlığı ve Hastalıkları Dergisi 2005;48:308-15.
19. Calik M, Aktas MS, Cecen E, Piskin IE, Ayaydın H, Ornek Z et al. The association between serum vitamin B12 deficiency and tension-type headache in Turkish children. Neurol Sci 2018;39(6):1009-14. doi: 10.1007/s10072-018-3286-5.
20. Altun H, Şahin N, Belge Kurutaş E, Güngör O. Homocysteine, Pyridoxine, Folate and Vitamin B12 Levels in Children with Attention Deficit Hyperactivity Disorder. Psychiatr Danub, 2018;30(3):310-6.
21. Meena MK, Sharma S, Bhasin H, Jain P, Kapoor S, Jain A et al. Vitamin B12 Deficiency in Children With Infantile Spasms: A Case-Control Study. Journal of Child Neurology 2018;33(12):767-71.
22. Ho M, Halim JH, Gow ML, El-Haddad N, Marzulli T, Baur LA et al. Vitamin B12 in Obese Adolescents with Clinical Features of Insulin Resistance. Nutrients 2014;6(12):5611-8. doi:10.3390/nu6125611.
23. Emen B, Kılıç Öztürk Y, Eren MA, Özdemir E, Öztürk F, Düzenli E et al. B12 Vitamin Eksikliği Bulunan Hastalarda Etiyolojik Faktörler İle Laboratuvar Verileri Arasındaki İlişkinin Geriye Dönük Değerlendirilmesi. Tepecik Eğit Hast Derg 2013;23(1):19-23.
24. VanderJagt DJ, Spelman K, Ambe J, Datta P, Blackwell W, Crossey M et. al. Folate and vitamin B12 status of adolescent girls in northern Nigeria. J Nat Med Assoc 2000;92:334-40.
25. Osifo BO, Lukanmbi FA, Bolodeoku JO. Reference values for serum folate, erythrocyte folate and serum cobalamin in Nigerian adolescents. Trop Geogr Med 1986;38:259-64.
26. Margalit I, Cohen E, Goldberg E, Krause I. Vitamin B12 Deficiency and the Role of Gender: A Cross-Sectional Study of a Large Cohort. Ann Nutr Metab 2018;72:265–71.
Kor, Deniz et al. “Mukopolisakkaridozlu Hastalarda Vitamin B12 düzeyleri”. Cukurova Medical Journal, vol. 45, no. 2, 2020, pp. 401-7, doi:10.17826/cumj.687569.