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Çocuklarda Vitamin B12 Eksikliğinin Metilmalonik Asit, Homosistein ve Holotranskobalamin ile Doğrulanması

Yıl 2023, Cilt: 25 Sayı: 2, 200 - 206, 31.08.2023

Serap Kirkiz Özlem Arman Bilir Fatih Mehmet Azık Çiğdem Sönmez Hüsniye Neşe Yaralı

https://doi.org/10.24938/kutfd.1263790

Öz

Amaç: Vitamin B12 eksikliği, çocuklarda yaygın bir sağlık sorunudur. Vitamin B12 eksikliğinin tanısı için serum vitamin B12 ölçümünün duyarlılığı düşük olmakla birlikte, erken ve doğru tanıda plazma metilmalonik asit, homosistein ve holotranskobalaminin kombine kullanımının daha spesifik biyobelirteçler olduğu bildirilmiştir. Bu çalışmada çocuklarda vitamin B12 eksikliğinin tanısını metilmalonik asit, homosistein ve holotranskobalamin ölçümü ile doğrulamak ve bu belirteçlerin doğruluğunu belirlemeyi amaçladık.

Gereç ve Yöntemler: Çalışmaya <18 yaş ve vitamin B12 düzeyi <200 pg/ml olan 277 hasta dahil edildi. Tüm hastalarda vitamin B12, metilmalonik asit, homosistein, holotranskobalamin düzeyleri değerlendirildi. Vitamin B12 eksikliğini tanımlamak için cut-off değerleri metilmalonik asit >0.4 μmol L, holotranskobalamin <21 pmol/L idi. Homosistein düzeyleri yaşa göre değerlendirildi.

Bulgular: Vitamin B12 ile holotranskobalamin arasında pozitif korelasyon (kappa indeksi 0.387), vitamin B12, metilmalonik asit ve homosistein arasında negatif korelasyon (kappa indeksi -0.134, kappa indeksi -0.258) görüldü. Metilmalonik asit ve holotranskobalamin, metilmalonik asit ve homosistein, homosistein ve holotranskobalamin arasında zayıf korelasyon izlendi (sırasıyla kappa indeksi -0.039, 0.243, -0.377). Hastalar holotranskobalamin, homosistein, metilmalonik asit seviyelerine göre 4 gruba ayrıldı. Yetmiş üç hastada (%26) holotranskobalamin düzeyi düşüktü. Grup 1a, vitamin B12 eksikliği tanısı alan ve her 3 parametre ile desteklenen 37 hastadan oluşuyordu. Tüm gruplar karşılaştırıldığında Grup 1a’nın vitamin B12 ve hemoglobin düzeyleri diğer gruplardan daha düşüktü (sırasıyla, p<0.05, p<0.001).

Sonuç: Çocuklarda, holotranskobalamin tek başına doğru bir gösterge olarak kabul edilmemeli ve vitamin B12 eksikliği tanısında diğer fonksiyonel belirteçler ile birlikte değerlendirilmelidir. Ayrıca, vitamin B12 eksikliği ile ilgili çalışmaların çoğu yetişkin yaş gruplarında yapılmıştır ve çocuklarda holotranskobalamin ve serum metilmalonik asit referans aralıklarını belirlemek için yeni çalışmalara ihtiyaç vardır.

Anahtar Kelimeler

Vitamin B12 metilmalonik asit holotranskobalamin

Kaynakça

  • Sobczyńska-Malefora A, Gorska R, Pelisser M, Ruwona P, Witchlow B, Harrington DJ. An audit of holotranscobalamin ("Active" B12) and methylmalonic acid assays for the assessment of vitamin B12 status: application in a mixed patient population. Clin Biochem. 2014;47(1-2):82-6.
  • Hogeveen M, van Beynum I, van Rooij A, Kluijtmans L, den Heijer M, Blom H. Methylmalonic acid values in healthy Dutch children. Eur J Nutr. 2008;47(1):26-31. 
  • Bjørke Monsen AL, Ueland PM. Homocysteine and methylmalonic acid in diagnosis and risk assessment from infancy to adolescence. Am J Clin Nutr. 2003;78(1):7-21.
  • Monagle PT, Tauro GP. Infantile megaloblastosis secondary to maternal vitamin B12 deficiency. Clin Lab Haematol. 1997;19(1):23-5. 
  • Karagöl C, Yiğit M. Evaluation of clinical and laboratory findings and diagnostic difficulties in children with vitamin B12 deficiency. Pediatric Practice and Research. 2022;10(1):1-5.
  • Kalay Z, Islek A, Parlak M, Kirecci A, Guney O, Koklu E, et al. Reliable and powerful laboratory markers of cobalamin deficiency in the newborn: Plasma and urinary methylmalonic acid. J Matern Fetal Neonatal Med. 2016;29(1):60-3. 
  • Dobson R, Alvares D. The difficulties with vitamin B12. Pract Neurol. 2016;16(4):308-11.
  • Green R. Vitamin B12 deficiency from the perspective of a practicing hematologist. Blood. 2017;129(19):2603-11.
  • Valente E, Scott JM, Ueland PM, Cunningham C, Casey M, Molloy AM. Diagnostic accuracy of holotranscobalamin, methylmalonic acid, serum cobalamin, and other indicators of tissue vitamin B₁₂ status in the elderly. Clin Chem. 2011;57(6):856-63.
  • Sobczyńska-Malefora A, Delvin E, McCaddon A, Ahmadi KR, Harrington DJ. Vitamin B12 status in health and disease: a critical review. Diagnosis of deficiency and insufficiency - clinical and laboratory pitfalls. Crit Rev Clin Lab Sci. 2021;58(6):399-429.
  • Al Aisari F, Al-Hashmi H, Mula-Abed WA. Comparison between serum holotranscobalamin and total vitamin B12 as ındicators of vitamin B12 status. Oman Med J. 2010;25(1):9-12.
  • Dastidar R, Sikder K. Diagnostic reliability of serum active B12 (holo-transcobalamin) in true evaluation of vitamin B12 deficiency: Relevance in current perspective. BMC Res Notes. 2022;15(1):329.
  • Altuntaş N, Soylu K, Suskan E, Akar N. Homocysteine levels in Turkish children. Turk J Haematol. 2004;21(2):79-82.
  • Lanzkowsky P. Hematological Reference Values. In: Lanzkowsky P, ed.  Manual of pediatric hematology and oncology. 5th ed. New York, USA. Elsevier Academic Press, 2011;971.
  • Vashi P, Edwin P, Popiel B, Lammersfeld C, Gupta D. Methylmalonic acid and homocysteine as ındicators of vitamin B-12 deficiency in cancer. PLoS One. 2016;11(1):e0147843.
  • Barlak Keti D, Muhtaroğlu S. Evaluation of the concordance between holotranscobalamin and vitamin B12 levels. Journal of Turkish Clinical Biochemistry. 2021;19(3):193-9.
  • Bondu JD, Nellickal AJ, Jeyaseelan L, Geethanjali FS. Assessing diagnostic accuracy of serum holotranscobalamin (Active-B12) in comparison with other markers of vitamin B12 deficiency. Indian J Clin Biochem. 2020;35(3):367-72.
  • Remacha AF, Sardà MP, Canals C, Queraltò JM, Zapico E, Remacha J, et al. Role of serum holotranscobalamin (holoTC) in the diagnosis of patients with low serum cobalamin. Comparison with methylmalonic acid and homocysteine. Ann Hematol. 2014;93(4):565-9. 
  • Herbert V. Staging vitamin B-12 (cobalamin) status in vegetarians. Am J Clin Nutr.1994; 59(5 Suppl):1213-22.
  • Rogers LM, Boy E, Miller JW, Green R, Sabel JC, Allen LH. High prevalence of cobalamin deficiency in Guatemalan schoolchildren: Associations with low plasma holotranscobalamin II and elevated serum methylmalonic acid and plasma homocysteine concentrations. Am J Clin Nutr. 2003;77(2):433-40.
  • Ok Bozkaya I, Yarali N, Kizilgün M, Ozkan S, Tunc B. Relationship between the levels of holotranscobalamin and vitamin B12 in children. Indian J Hematol Blood Transfus. 2017;33(4):537-40.
  • Heiner-Fokkema MR, Riphagen IJ, Wiersema NS, van Zanden JJ, Kootstra-Ros JE, Pinxterhuis TH, et al. Age dependency of plasma vitamin B12 status markers in Dutch children and adolescents. Pediatr Res. 2021;90(5):1058-64.

DIAGNOSIS OF VITAMIN B12 DEFICIENCY IN CHILDREN BY USING METHYLMALONIC ACID, HOMOCYSTEINE AND HOLOTRANSCOBALAMINE

Yıl 2023, Cilt: 25 Sayı: 2, 200 - 206, 31.08.2023

Serap Kirkiz Özlem Arman Bilir Fatih Mehmet Azık Çiğdem Sönmez Hüsniye Neşe Yaralı

https://doi.org/10.24938/kutfd.1263790

Öz

Objective: Vitamin B12 deficiency is a common health issue in children. Though the sensivity of serum vitamin B12 measurement for the diagnosis of vitamin B12 deficiency is low, combined methylmalonic acid, homocysteine and holotranscobalamin have been reported to be more specific biomarkers in early and accurate diagnosis. In this study, we aimed to verify the diagnosis of vitamin B12 deficiency in children by measuring methylmalonic acid, homocysteine, holotranscobalamin and to determine the accuracy of them.

Material and Methods: The study included 277 patients aged <18 years old age and with a vitamin B12 levels <200 pg/ml. The cut-off values for defining vitamin B12 deficiency were methylmalonic acid>0.4 μmol L, holotranscobalamin <21 pmol/L. Homocysteine levels were evaluated according to age.

Results: There was a positive correlation (kappa index 0.387) between vitamin B12 and holotranscobalamin and a negative correlation between vitamin B12, methylmalonic acid and homocysteine levels (kappa index -0.134, -0.258, respectively). There was a weak correlation between methylmalonic acid and holotranscobalamin; methylmalonic acid and homocysteine; homocysteine and holotranscobalamin (kappa index -0.039, 0.243, -0.377, respectively). Patients were divided into 4 groups according to holotranscobalamin, homocysteine and methylmalonic acid levels.

Seventy-three patients (26%) had low holotranscobalamin. Group 1a was consisting of 37 patients who were diagnosed vitamin B12 deficiency with low serum B12 and supported by all 3 parameters. When all groups were compared, vitamin B12 and hemoglobin levels were found to be lower in Group 1a than other groups (respectively, p<0.05, p<0.001)

Conclusion: In children, holotranscobalamin alone should not be considered an accurate indicator, and other functional markers should be combined in the diagnosis of vitamin B12 deficiency. Furthermore, most studies about vitamin B12 deficiency were carried out in adult age groups, and studies are needed in children to determine the reference intervals for holotranscobalamin and serum methylmalonic acid.

Anahtar Kelimeler

Vitamin B12 methylmalonic acid holotranscobalamin

Destekleyen Kurum

This research did not receive any specific grant from funding agencies in the public,commercial, or not-for-profit sectors.

Kaynakça

  • Sobczyńska-Malefora A, Gorska R, Pelisser M, Ruwona P, Witchlow B, Harrington DJ. An audit of holotranscobalamin ("Active" B12) and methylmalonic acid assays for the assessment of vitamin B12 status: application in a mixed patient population. Clin Biochem. 2014;47(1-2):82-6.
  • Hogeveen M, van Beynum I, van Rooij A, Kluijtmans L, den Heijer M, Blom H. Methylmalonic acid values in healthy Dutch children. Eur J Nutr. 2008;47(1):26-31. 
  • Bjørke Monsen AL, Ueland PM. Homocysteine and methylmalonic acid in diagnosis and risk assessment from infancy to adolescence. Am J Clin Nutr. 2003;78(1):7-21.
  • Monagle PT, Tauro GP. Infantile megaloblastosis secondary to maternal vitamin B12 deficiency. Clin Lab Haematol. 1997;19(1):23-5. 
  • Karagöl C, Yiğit M. Evaluation of clinical and laboratory findings and diagnostic difficulties in children with vitamin B12 deficiency. Pediatric Practice and Research. 2022;10(1):1-5.
  • Kalay Z, Islek A, Parlak M, Kirecci A, Guney O, Koklu E, et al. Reliable and powerful laboratory markers of cobalamin deficiency in the newborn: Plasma and urinary methylmalonic acid. J Matern Fetal Neonatal Med. 2016;29(1):60-3. 
  • Dobson R, Alvares D. The difficulties with vitamin B12. Pract Neurol. 2016;16(4):308-11.
  • Green R. Vitamin B12 deficiency from the perspective of a practicing hematologist. Blood. 2017;129(19):2603-11.
  • Valente E, Scott JM, Ueland PM, Cunningham C, Casey M, Molloy AM. Diagnostic accuracy of holotranscobalamin, methylmalonic acid, serum cobalamin, and other indicators of tissue vitamin B₁₂ status in the elderly. Clin Chem. 2011;57(6):856-63.
  • Sobczyńska-Malefora A, Delvin E, McCaddon A, Ahmadi KR, Harrington DJ. Vitamin B12 status in health and disease: a critical review. Diagnosis of deficiency and insufficiency - clinical and laboratory pitfalls. Crit Rev Clin Lab Sci. 2021;58(6):399-429.
  • Al Aisari F, Al-Hashmi H, Mula-Abed WA. Comparison between serum holotranscobalamin and total vitamin B12 as ındicators of vitamin B12 status. Oman Med J. 2010;25(1):9-12.
  • Dastidar R, Sikder K. Diagnostic reliability of serum active B12 (holo-transcobalamin) in true evaluation of vitamin B12 deficiency: Relevance in current perspective. BMC Res Notes. 2022;15(1):329.
  • Altuntaş N, Soylu K, Suskan E, Akar N. Homocysteine levels in Turkish children. Turk J Haematol. 2004;21(2):79-82.
  • Lanzkowsky P. Hematological Reference Values. In: Lanzkowsky P, ed.  Manual of pediatric hematology and oncology. 5th ed. New York, USA. Elsevier Academic Press, 2011;971.
  • Vashi P, Edwin P, Popiel B, Lammersfeld C, Gupta D. Methylmalonic acid and homocysteine as ındicators of vitamin B-12 deficiency in cancer. PLoS One. 2016;11(1):e0147843.
  • Barlak Keti D, Muhtaroğlu S. Evaluation of the concordance between holotranscobalamin and vitamin B12 levels. Journal of Turkish Clinical Biochemistry. 2021;19(3):193-9.
  • Bondu JD, Nellickal AJ, Jeyaseelan L, Geethanjali FS. Assessing diagnostic accuracy of serum holotranscobalamin (Active-B12) in comparison with other markers of vitamin B12 deficiency. Indian J Clin Biochem. 2020;35(3):367-72.
  • Remacha AF, Sardà MP, Canals C, Queraltò JM, Zapico E, Remacha J, et al. Role of serum holotranscobalamin (holoTC) in the diagnosis of patients with low serum cobalamin. Comparison with methylmalonic acid and homocysteine. Ann Hematol. 2014;93(4):565-9. 
  • Herbert V. Staging vitamin B-12 (cobalamin) status in vegetarians. Am J Clin Nutr.1994; 59(5 Suppl):1213-22.
  • Rogers LM, Boy E, Miller JW, Green R, Sabel JC, Allen LH. High prevalence of cobalamin deficiency in Guatemalan schoolchildren: Associations with low plasma holotranscobalamin II and elevated serum methylmalonic acid and plasma homocysteine concentrations. Am J Clin Nutr. 2003;77(2):433-40.
  • Ok Bozkaya I, Yarali N, Kizilgün M, Ozkan S, Tunc B. Relationship between the levels of holotranscobalamin and vitamin B12 in children. Indian J Hematol Blood Transfus. 2017;33(4):537-40.
  • Heiner-Fokkema MR, Riphagen IJ, Wiersema NS, van Zanden JJ, Kootstra-Ros JE, Pinxterhuis TH, et al. Age dependency of plasma vitamin B12 status markers in Dutch children and adolescents. Pediatr Res. 2021;90(5):1058-64.
Toplam 22 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Sağlık Kurumları Yönetimi
Bölüm Özgün Araştırma
Yazarlar

Serap Kirkiz 0000-0002-3885-5325

Özlem Arman Bilir 0000-0001-8316-3603

Fatih Mehmet Azık 0000-0001-5715-4244

Çiğdem Sönmez 0000-0001-9307-5674

Hüsniye Neşe Yaralı 0000-0001-5488-2385

Yayımlanma Tarihi 31 Ağustos 2023
Gönderilme Tarihi 11 Mart 2023
Yayımlandığı Sayı Yıl 2023 Cilt: 25 Sayı: 2

Kaynak Göster

APA Kirkiz, S., Arman Bilir, Ö., Azık, F. M., Sönmez, Ç., vd. (2023). DIAGNOSIS OF VITAMIN B12 DEFICIENCY IN CHILDREN BY USING METHYLMALONIC ACID, HOMOCYSTEINE AND HOLOTRANSCOBALAMINE. Kırıkkale Üniversitesi Tıp Fakültesi Dergisi, 25(2), 200-206. https://doi.org/10.24938/kutfd.1263790
AMA Kirkiz S, Arman Bilir Ö, Azık FM, Sönmez Ç, Yaralı HN. DIAGNOSIS OF VITAMIN B12 DEFICIENCY IN CHILDREN BY USING METHYLMALONIC ACID, HOMOCYSTEINE AND HOLOTRANSCOBALAMINE. Kırıkkale Üni Tıp Derg. Ağustos 2023;25(2):200-206. doi:10.24938/kutfd.1263790
Chicago Kirkiz, Serap, Özlem Arman Bilir, Fatih Mehmet Azık, Çiğdem Sönmez, ve Hüsniye Neşe Yaralı. “DIAGNOSIS OF VITAMIN B12 DEFICIENCY IN CHILDREN BY USING METHYLMALONIC ACID, HOMOCYSTEINE AND HOLOTRANSCOBALAMINE”. Kırıkkale Üniversitesi Tıp Fakültesi Dergisi 25, sy. 2 (Ağustos 2023): 200-206. https://doi.org/10.24938/kutfd.1263790.
EndNote Kirkiz S, Arman Bilir Ö, Azık FM, Sönmez Ç, Yaralı HN (01 Ağustos 2023) DIAGNOSIS OF VITAMIN B12 DEFICIENCY IN CHILDREN BY USING METHYLMALONIC ACID, HOMOCYSTEINE AND HOLOTRANSCOBALAMINE. Kırıkkale Üniversitesi Tıp Fakültesi Dergisi 25 2 200–206.
IEEE S. Kirkiz, Ö. Arman Bilir, F. M. Azık, Ç. Sönmez, ve H. N. Yaralı, “DIAGNOSIS OF VITAMIN B12 DEFICIENCY IN CHILDREN BY USING METHYLMALONIC ACID, HOMOCYSTEINE AND HOLOTRANSCOBALAMINE”, Kırıkkale Üni Tıp Derg, c. 25, sy. 2, ss. 200–206, 2023, doi: 10.24938/kutfd.1263790.
ISNAD Kirkiz, Serap vd. “DIAGNOSIS OF VITAMIN B12 DEFICIENCY IN CHILDREN BY USING METHYLMALONIC ACID, HOMOCYSTEINE AND HOLOTRANSCOBALAMINE”. Kırıkkale Üniversitesi Tıp Fakültesi Dergisi 25/2 (Ağustos 2023), 200-206. https://doi.org/10.24938/kutfd.1263790.
JAMA Kirkiz S, Arman Bilir Ö, Azık FM, Sönmez Ç, Yaralı HN. DIAGNOSIS OF VITAMIN B12 DEFICIENCY IN CHILDREN BY USING METHYLMALONIC ACID, HOMOCYSTEINE AND HOLOTRANSCOBALAMINE. Kırıkkale Üni Tıp Derg. 2023;25:200–206.
MLA Kirkiz, Serap vd. “DIAGNOSIS OF VITAMIN B12 DEFICIENCY IN CHILDREN BY USING METHYLMALONIC ACID, HOMOCYSTEINE AND HOLOTRANSCOBALAMINE”. Kırıkkale Üniversitesi Tıp Fakültesi Dergisi, c. 25, sy. 2, 2023, ss. 200-6, doi:10.24938/kutfd.1263790.
Vancouver Kirkiz S, Arman Bilir Ö, Azık FM, Sönmez Ç, Yaralı HN. DIAGNOSIS OF VITAMIN B12 DEFICIENCY IN CHILDREN BY USING METHYLMALONIC ACID, HOMOCYSTEINE AND HOLOTRANSCOBALAMINE. Kırıkkale Üni Tıp Derg. 2023;25(2):200-6.
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