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

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

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

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

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