Lower extremity amputation in a preterm infant due to MTHFR homozygosity.

Neonatal thrombosis of the extremities is a rare clinical condition that can cause serious problems. Predisposing factors are well defined such as maternal diabetes, polycythemia, congenital cardiac malformations, umbilical artery catheterization, prematurity, asphyxia, necrotizing enterocolitis, sepsis, and hereditary thrombophilie disorders (6, 8, 12, 15). The methylenetetrahydrofolate reductase (MTHFR) enzyme has a critical role in homocysteine metabolism. Homozygosity for the C667T allele of MTHFR act synergistically with other congenital or acquired predisposing factors and may cause severe thromboembolic events (14).A male infant weighing 700 g was bom via emergency cesarean section due to early membrane rupture at 26 weeks of gestational age with an APGAR score 4 at 1 min and 7 at 5 min. The mother was a 33 years-old, gravida 3, para 2 and abortion 1 woman. Family history was negative for both early or late thromboembolic events and recurrent abortions. The patient was admitted to the neonatal intensive care unit after intubation and surfactant (Curosurf®) therapy.Both arterial and venous umbilical catheterizations were performed. Six hours after the placement of the arterial catheter, cyanosis was started at the fingertips of the right lower extremity and progressed proximally. The popliteal and posterior tibial arterial pulses were absent on physical examination. Capillary refill time was prolonged in comparison with the other extremities. The oxygen saturation could not be detected by pulse oximeter in the right lower extremity while it was higher than 85% in the other measurement sites of the body. Despite the removal of the catheter, ischemic signs progressed. Doppler examination demonstrated a thrombotic occlusion in the popliteal artery while venous examination was normal.Coagulation test panel revealed that prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalized ratio (INR), protein C and S levels, Factors 8,9 and 11, fibrinogen and antithrombin III activity were within normal ranges. Activated protein C resistance test, antiphospholipid and anticardiolipin antibodies were negative. The serum homocysteine level was high: 13.1 mmol/L (N: Afterwards, low molecular weight heparin (LMWH) was administered for antithrombotic treatment with monitoring anti-Xa level. Additionally, tissue plasminogen activator (tPA) was administered with parental consent as thrombolytic therapy because of an acute extremity-threatening vascular occlusion. Moreover, topical nitroglycerin ointment was applied for every six hours to increase perfusion of the extremity. Unfortunately, the ischemia did not resolve and rapidly progressed to gangrene (Fig. 1). On the 9th day of life, after the maturation of the demarcation line, below-knee amputation was performed. Transtibial amputation was done with preserving the largest bone possible as the soft-tissue coverage permits. The stump was covered with myoplasty and skin was closed with side-to-side mattress sutures. The wound was healed with daily care and there were no wound-related complications (Fig. 2). A rapid clinical improvement was noted after the surgery. The patient was extubated to continuous positive airway pressure on the 14lh day. After the administration of full enteral feeding, the patient was discharged on postnatal 95,h day.The prevalence of symptomatic arterial thrombosis is approximately 1 in 20000-40000 birth and reaches from 2.4 to 6.8 in 1000 for neonates in intensive care unit (2,13, 16). About 90 % of the thromboembolic events are associated with arterial or venous catheterization (6, 12). Several congenital, acquired, inherited and maternal risk factors have been described for spontaneous and catheter induced neonatal thromboembolism. …