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Clin Biochem. 2003 Jun;36(4):275-82.

Urine methylmalonic acid measurements for the assessment of cobalamin deficiency related to neuropsychiatric disorders.

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GATA Haydarpaşa Educational Hospital Biochemistry Department 81327 Kadikoy/Istanbul, Turkey.



Detection of cobalamin deficiency is clinically important for a better understanding of neuropsychiatric diseases, and why the deficiency occurs more frequently than previously anticipated. However, serum cobalamin measurements have a limited ability to diagnose a deficiency state.


To evaluate functional cobalamin status in neuropsychiatric patients using an appropriate photometric urine methylmalonic acid (MMA) determination method that could be easily adapted to all routine clinical laboratories.


We modified the old photometric method used for determining urinary MMA concentrations. MMA measurements were made in first morning urine samples with normalizing by creatinine concentrations. The serum cobalamin, total homocysteine (tHcy), folate, red cell folate, and urinary MMA concentrations taken from 17 psychosis, 28 depression, 16 dementia patients and 47 healthy people were analyzed using the ROC, correlation and multiple regression analysis.


The modified method was found to have better recovery (96-103%) and CV% values than the old method. Mean +/- SDs of uMMA and cobalamin concentrations were 11.49 +/- 4.93 mmol/mol creatinine, and 231 +/- 151 pg/mL in psychosis and depression group, and 6.04 +/- 1.93 mmol/mol creatinine and 308 +/- 140 pg/mL in control group, respectively. Those in the dementia group were 11.53 +/- 4.0 mmol/mol creatinine and 231 +/- 84 pg/mL, and in the control group 6.05 +/- 1.94 mmol/mol creatinine and 364 +/- 188 pg/mL. There was a good correlation between urinary MMA and serum Vitamin B(12) determinations for all groups at a confidence level (p) of 99%. The correlation between urinary MMA and red cell folate was also significant at p = 95% for depression, psychosis and control groups, and p = 99% for dementia group. In the ROC analyses, area under the curve values for uMMA, B12 and tHcy were 0.842, 0.796 and 0.728, respectively.


A sensitive and easy photometric method has been presented. When cobalamin deficiency is suspected in neuropsychiatric patients, photometric urinary MMA determination analysis can be the first diagnostic test used. If the urinary MMA concentration is above the reference value, serum cobalamin levels can be determined for further diagnosis.

[Indexed for MEDLINE]

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