title: The 677C --> T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in epileptic patients affected by systemic lupus erythematosus.
abstract: Neuropsychiatric involvement in systemic lupus erythematosus (NPSLE) is considered as one of the major manifestations of the disease. Epilepsy has been documented in about 10% of patients with systemic lupus erythematosus (SLE). It is well known that vascular damage in SLE occurs because of multiple mechanisms including hypercoagulation. It has been recently reported that in SLE patients raised levels of homocysteine are associated with arterial thrombosis. Hyperhomocysteinaemia is a condition due to both genetic and non-genetic factors. The most common genetic defect in homocysteine metabolism is a decreased activity of a common 5,10-methylenetetrahydrofolate reductase (MTHFR) variant (677C -->T, a thermolabile form). In this paper we describe the epileptic manifestations in six out of 55 SLE patients. Seizures were the SLE onset symptom for three patients, appeared during the active disease in two cases, and occurred during a period of clinical remission in one patient. In all cases we documented the association of epilepsy with the MTHFR mutation: the homozygosity form was present in one case (16.7%), and heterozygosity in five cases (83.3%). Nevertheless, levels of homocysteine in plasma were in the normal range. Moreover, we found a decrease in the level of S protein values in one case, a high titre positivity of anticardiolipin antibodies (aCL) (IgG and IgM) in three patients and low titre positivity (IgG) in one patient, and lupus anticoagulant (LAC) positivity in four cases. In conclusion, we believe that the abnormalities of coagulation present in our patients could be related to epileptogenesis or to an alteration of the seizure threshold.
authors.affiliation: Department of Clinical Medicine, First Faculty of Medicine, University of Rome La Sapienza, Rome, Italy. aafeltra@tin.it
authors.forename: Antonella
authors.initials: A
authors.lastname: Afeltra
authors.forename: Antonio
authors.initials: A
authors.lastname: Amoroso
authors.forename: Anna Paola
authors.initials: AP
authors.lastname: Mitterhofer
authors.forename: Marta
authors.initials: M
authors.lastname: Vadacca
authors.forename: Sara
authors.initials: S
authors.lastname: Galluzzo
authors.forename: Ada
authors.initials: A
authors.lastname: Francia
authors.forename: Flavia
authors.initials: F
authors.lastname: Del Porto
authors.forename: Giuseppe Maria
authors.initials: GM
authors.lastname: Gandolfo
mesh_terms: D000293:Adolescent; D000328:Adult; D017153:Antibodies, Anticardiolipin / Q000276:immunology; D004827:Epilepsy / Q000150:complications* / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D006710:Homocysteine / Q000097:blood; D006720:Homozygote; D006801:Humans; D020138:Hyperhomocysteinemia / Q000235:genetics / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D016682:Lupus Coagulation Inhibitor / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000150:complications* / Q000276:immunology / Q000378:metabolism; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics*; D017293:Protein S / Q000378:metabolism
chemical_list: D017153:Antibodies, Anticardiolipin; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D016682:Lupus Coagulation Inhibitor; D017293:Protein S; D006710:Homocysteine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)