TRMA can be observed anytime between infancy and adolescence and usually all the cardinal findings are not present at the beginning
1-4. Although diabetes mellitus, deafness and anemia are the clinical traid of the TRMA, other clinical symptoms or signs such as arythmias, congenital heart disease, abnormalities of the retina and aminoaciduria are also reported. Although they are seen only in a few cases stroke or stroke like episodes are certain features of TRMA. Shaw-Smith et al
8 reported that stroke occurred in 4/30 (13%) of patients in a previous study with 30 patients. Villa et al
9 reported a 20 years old woman with TRMA admitted to hospital because of acute ischemic stroke. They have reported that stroke might be due to the oral contraceptive that the patient used previously. We considered TRMA in our patient because of megaloblastic anemia, hyperglycemia, arrhytmia and stroke. Gene analysis confirmed our diagnosis since TRMA related SLC19A2 mutation was shown.
Fullerton et al 10 risk factors in children with recurrent ischemic stroke; children receiving antithrombotic therapy, arteriopathies, cardiac embolism, moyamoya disease, arteriel disection and infections as shown. They defined the greatest risk as arteriopathy. Our patient had two stroke attacks in different locations without any signs of arteriopathy. He was not under antithrombotic therapy. Since his echocardiography was in normal ranges we ruled out cardiac embolism. That’s why we primarily suspected the hematological etiologies in the differentional diagnosis of recurrent stroke. While investigating the etiology of stroke, homozygote MTHFR C677 and heterozygote MTHFR A1298 mutations were detected in his thrombosis panel. Normal values of serum biochemistry and other thrombosis panel were estabilished. Especially in the presence of low serum folate levels reduced enzyme activity of MTHFR is considered a genetic risk factor for hyperhomocysteinemia. However mild to moderate hyperhomocysteinemia has been identified as one of the risk factors for venous thrombosis and it has also been associated with other cardiovascular diseases, like coronary artery disease. In general, the genotypes below at the moment appear unlikely to to have clinical significance: “thermolabile” variant c.665C→T heterozygote, c.1286A→C homozygote, or (c.665C→T); (c.1286A→C) compound heterozygot 11. There is theoretical reason to consider that the rare individuals with triple variant MTHFR genotypes (i.e, individuals who are homozygous for one variant and heterozygous for the other) may have clinical risks, although that is currently speculative.
As far as we know our patient is the first case in the literature with recurrent stroke and a mutation in SLC19A2 gene besides two more mutations that may cause thrombosis. In TRMA no recurrent ischemic stroke attacks due to other thrombotic factors were defined before our case. In patients with stroke TRMA should be considered in differential diagnosis. Hovewer in TRMA patients especially with stroke, the other congenital risk factors should also be investigated.
