2003•Hemodialysis InternationalRequires access

Methylmalonic Acid in Dialysis Patients

Lukáš Svoboda, L. Stráník, J Hyánek, František Pehal

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Abstract

Propionyl-CoA is a common product of metabolism of essential AA (Val, Thr, Leu, Ile), fatty acids and cholesterol and is further metabolised enzymatically to methyl-malonyl CoA, which is further isomerised to succinyl CoA. Because of the common cofactor (cobalamin) methylmalonic acid (Mma) can serve as an early marker of functional cobalamin deficiency. Purpose of the study: To evaluate possible hidden cobalamin deficiency and the effect of treatment with iv. vit B12 on Mma and tot. homocystein (tHcy) levels in dialysis patients (pts). Methods: 48 HD treated pts, in routine medication folic acid 5 mg/d, pyridoxin 20 mg/d. Measurement of serum levels of Mmk, folic acid, tHcy, cobalamin, blood counts. Healthy patients served as controls for Mma. Vit B12 therapy – cyanocobalamin 1 mg iv. after HD every week for 6 weeks, after 6 weeks 1mg monthly. Results: HD patients: before B12 treatment after B12 Methylmalonic acid 0,904 +/− 0,389 0,554 +/− 0,222 Total homocystein 21,653 +/− 6,851 16,055 +/− 4,896 Mma in EPO treated pts: 0,842 +/− 0,325 0,536 +/− 0,234 Mma in EPO non-treated: 1,028 +/− 0,482 0,590 +/− 0,199 Healthy controls: Mma = 0,305 +/− 0,158 umol/l (max. norm. 0,22) Conclusions: We did not find overt vitamin B12 deficiency in HD pts, however elevated levels of Mma and tHcy raise a question about functional B12 deficiency. Vitamin B12 supplementation improved (decreased) the levels of both methylmalonic acid and homocystein in this subset of patients. Influence of EPO treatment merits further study.

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Propionyl-CoA is a common product of metabolism of essential AA (Val, Thr, Leu, Ile), fatty acids and cholesterol and is further metabolised enzymatically to methyl-malonyl CoA, which is further isomerised to succinyl CoA. Because of the common cofactor (cobalamin) methylmalonic acid (Mma) can serve as an early marker of functional cobalamin deficiency. Purpose of the study: To evaluate possible hidden cobalamin deficiency and the effect of treatment with iv. vit B12 on Mma and tot. homocystein (tHcy) levels in dialysis patients (pts). Methods: 48 HD treated pts, in routine medication folic acid 5 mg/d, pyridoxin 20 mg/d. Measurement of serum levels of Mmk, folic acid, tHcy, cobalamin, blood counts. Healthy patients served as controls for Mma. Vit B12 therapy – cyanocobalamin 1 mg iv. after HD every week for 6 weeks, after 6 weeks 1mg monthly. Results: HD patients: before B12 treatment after B12 Methylmalonic acid 0,904 +/− 0,389 0,554 +/− 0,222 Total homocystein 21,653 +/− 6,851 16,055 +/− 4,896 Mma in EPO treated pts: 0,842 +/− 0,325 0,536 +/− 0,234 Mma in EPO non-treated: 1,028 +/− 0,482 0,590 +/− 0,199 Healthy controls: Mma = 0,305 +/− 0,158 umol/l (max. norm. 0,22) Conclusions: We did not find overt vitamin B12 deficiency in HD pts, however elevated levels of Mma and tHcy raise a question about functional B12 deficiency. Vitamin B12 supplementation improved (decreased) the levels of both methylmalonic acid and homocystein in this subset of patients. Influence of EPO treatment merits further study.

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Available abstract

Propionyl-CoA is a common product of metabolism of essential AA (Val, Thr, Leu, Ile), fatty acids and cholesterol and is further metabolised enzymatically to methyl-malonyl CoA, which is further isomerised to succinyl CoA. Because of the common cofactor (cobalamin) methylmalonic acid (Mma) can serve as an early marker of functional cobalamin deficiency. Purpose of the study: To evaluate possible hidden cobalamin deficiency and the effect of treatment with iv. vit B12 on Mma and tot. homocystein (tHcy) levels in dialysis patients (pts). Methods: 48 HD treated pts, in routine medication folic acid 5 mg/d, pyridoxin 20 mg/d. Measurement of serum levels of Mmk, folic acid, tHcy, cobalamin, blood counts. Healthy patients served as controls for Mma. Vit B12 therapy – cyanocobalamin 1 mg iv. after HD every week for 6 weeks, after 6 weeks 1mg monthly. Results: HD patients: before B12 treatment after B12 Methylmalonic acid 0,904 +/− 0,389 0,554 +/− 0,222 Total homocystein 21,653 +/− 6,851 16,055 +/− 4,896 Mma in EPO treated pts: 0,842 +/− 0,325 0,536 +/− 0,234 Mma in EPO non-treated: 1,028 +/− 0,482 0,590 +/− 0,199 Healthy controls: Mma = 0,305 +/− 0,158 umol/l (max. norm. 0,22) Conclusions: We did not find overt vitamin B12 deficiency in HD pts, however elevated levels of Mma and tHcy raise a question about functional B12 deficiency. Vitamin B12 supplementation improved (decreased) the levels of both methylmalonic acid and homocystein in this subset of patients. Influence of EPO treatment merits further study.

Key concepts: Methylmalonic acid, Cobalamin, Vitamin B12, Cyanocobalamin, Medicine, Internal medicine, Hyperhomocysteinemia, Methylcobalamin

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