Cerebral infarct associated with prothrombin gene G 20210 A variant in a Turkish child with cystic fibrosis: an unusual coexistence

To the Editor: Cystic fibrosis (CF) is an autosomal recessively inherited disease characterized with pancreatic insufficiency and chronic lung disease (1). Coagulation abnormalities may sometimes occur in CF and generally manifest as bleeding symptoms, related to decreased vitamin K dependent factors and in a lesser frequency due to increased fibrinolytic activity (2, 3) . Here we describe an unusual case with CF who developed a cerebral infarct, which seemed to be contributed by the presence of prothrombin gene G 20210 A variant, that has recently been shown to be a genetic risk factor for thromboembolism (4-7). A 14-month female infant was presented as unconscious. She had experienced an abrupt onset of convulsions 4 d before presentation. She was given diazepam and luminalized in a local hospital and referred to our center when she had become unconscious. In her past history she had meconium ileus at birth. Her parents were unconsanguineous. At the age of 2.5 months she was admitted to our hospital because of repeated pulmonary infections and diarrhea. The diagnosis of CF was established on the basis of sweat chloride concentrations > 100 mEq/l(13O-160 mEq/l) on numerous occasions. She was given supplemental pancreatic enzymes, fatsoluble vitamins and prophylactic antibiotic therapy. On this admission, although she seemed to be unconscious she was responsive to painful stimuli caused by moving her extremities. The pupils were isochoric and responsive to light. Except for her neurologic compromise all other physical examination findings were normal. There was no notified event such as a recent trauma or a family history that might have been relevant to her neurological status. Complete blood count findings, determination of serum electrolytes, glucose and calcium levels, liver and renal function tests, urine and cerebro-spinal fluid (CSF) analysis were all normal. Blood, urine and CSF cultures were sterile. Cardiac examination and echocardiography showed no abnormality. An electroencephalograph record showed active paroxismal activity originating from the left occipital region. Cerebral MRI revealed an infarcted area in the right parietotemporal region. Since neither evidence of a mass effect as seen in an acute infarct nor a volume loss due to encephalomalasia as defined in a chronic infarct was present, the lesion seen in MRI was diagnosed to be a subacute infarct (Fig. 1). In coagulation screening her PT was 11.40 s (N=11-14 s) and her APTT was 32.60 s (N=2540 s); protein C, protein S, antithrombin I11 and fibrinogen were all found to be normal. Anticardiolipin antibodies were negative. Heterozygosity for prothrombin gene G 20210 A variant was found by amplification of prothrombin gene (Factor 11) by polymerase chain reaction (PCR) and using a method described elsewhere (4). Over the following days her neurologic status improved partially. She was put on prophylactic coumadin therapy and discharged with some residual neurologic compromise, with an invitation to periodic controls. Coagulation abnormalities may sometimes occur in patients with CF. In patients with advanced pulmonary disease who have impaired liver functions and/or hepatosplenomegaly and malabsorption, decreased levels of vitamin K dependent factors (prothrombin and factor VII-X complex) may contribute to prolonged PT and PTT. Increased fibrinolytic activity and a mild thrombocytopenia due to hypersplenism were also reported in some children with CF (2). Coagulation abnormalities generally manifest as bleeding symptoms, and a thromboembolic phenomenon is quite uncommon in CF. Although protein C and protein S are also vitamin K dependent natural anticoagulants, thromboembolism related to their deficiency is not a defined complication in CF. In our patient the disease (CF) has been succesfully controlled. She was put on a supplemental therapy consisting of pancreatic enzymes