PB1964 ROLE OF HOMOCYSTEINE AND METHILMALONIC ACID IN NEUROLOGICAL PATHOLOGY
Authors: M.A. Legarda Campo, S. Payán‐Pernía, L. Querol, J. Martí Fàbregas, V. Criado Casas, X. Sales García, M. Serra Ferrer, M.P. Sardá, E. Zapico, A.F. Remacha Sevilla
Journal: HemaSphere (2019)

Background: Vitamin B 12 (B 12 ) deficiency causes hematological and non‐hematological disorders. The latter include neurological syndromes such as polyneuropathies, subacute combined degeneration, basal ganglia lesions, dementia or ischemic stroke. These symptoms can be present even in the absence of anemia or macrocytosis, and the lack of these hematologic changes cannot exclude B 12 deficiency as a cause of neurological symptoms.. There may be deficiency of B 12 with normal or borderline serum levels, hence the relevance of assessing its metabolites homocysteine (HCY) and methylmalonic acid (MMA), that increase in case of B 12 deficiency. Aims: To determine the value of HCY and MMA in the diagnosis of B 12 deficiency in patients with neurological symptoms. Methods: A retrospective analysis of the cases in which evaluation of B 12 and folic acid was requested from the Neurology department during a period of thirteen months was performed. Analytical (complete blood count –CBC–, serum B 12 , serum folate, erythrocyte folate –when serum folate was low–, HCY, MMA, serum creatinine and estimated glomerular filtration rate –eGFR–) and demographic parameters were evaluated. B 12 levels under 150 pg/L were considered low (LB 12 ); between 150 and 200 pmol/L, borderline (BB 12 ); and higher than 200 pmol/L, normal (NB 12 ). Results: One thousand thirty nine (7.8%) of the 14644 requests came from the Neurology department. LB 12 was found in 101 (9%) of these cases, BB 12 in 177 (15.5%) and NB 12 in 861 (75.6%). Folate deficiency was found in 11 (1%) patients. Regarding to patients with LB 12 , 62% had no alterations in the CBC, 25% had non‐macrocytic anemia and 8% had macrocytic anemia or macrocitosis. These results were similar in the group with BB 12 . Considering the patients with NB 12 , 72% of them had a normal CBC, 11,5% had non‐macrocytic anemia, and macrocytic anemia or macrocytosis was observed in 6%. Hematological alterations in these three groups were mild or moderate in 90% of cases; in none was severe (considered if hemoglobin &lt;7 gr/dL, platelets &lt;50x10e9/L, neutrophils &lt;0.5x10e9/L). The metabolite levels were available in 162 cases of the NB 12 group. In these patients, high HCY (&gt;14.5 umol/L) was found in 18.8%. Folate levels were normal for all of them, although 32% had an abnormal eGFR that may contribute to the increase in HCY. Mutational status of the MTHFR gene is unknown in these patients. MMA was measured in 7.8% of the patients with NB 12 ; increased levels (&gt;0.4 umol/L) were found in 23.5%. In the NB 12 group, 10 patients showed an increase in both metabolites (table 1), suggesting an actual B 12 deficiency despite the normal B 12 levels. Sensory polyneuropathy was the neurological finding in 9 of these patients and B 12 deficiency was assumed the cause in 4 of them, who were given supplementary treatment. Summary/Conclusion: The incidence of B 12 deficiency in patients with neurological symptoms is high. Most of these B 12 ‐deficient patients did not show hematological changes or these were mild, and some of them presented with normal serum B 12 . Assessment of the metabolites is essential in these patients with normal serum B 12 and neurological symptoms. This situation represents a true diagnostic and therapeutic challenge. image Therefore, in the context of a high clinical suspicion, a normal or borderline B 12 does not rule out a functional deficiency and metabolites should be assessed.