The case of a 48-year-old male patient whose father had died from a stroke is reported. The patient had a personal history of HBP, dyslipidemia and former smoking. In 1994 he experienced an inferolateral non-Q wave AMI, and in 2001 he was admitted to hospital for an ischemic stroke. He was then diagnosed a mutation in the prothrombin (FII 20210) and methylenetetrahydrofolate reductase (MTHFR) genes, with normal homocysteine levels. Patient was again admitted to hospital in 2002 for non-Q wave AMI. He was being treated wit ramipril, acetyl salicylic acid, omeprazole, pravastatin, and metoprolol.
He attended the emergency room for a sudden, continuous pain in the periumbilical region and right flank
for the past 72 hours. Pain was irradiated to the right renal fossa and associated to nausea, vomiting, and dark urine.
Physical examination revealed abdominal tenderness in the periumbilical region and right flank.
Laboratory tests showed elevated GOT, GPT, and LDH levels with normal renal function, electrolytes, and coagulation. Urine analysis found proteinuria (30 mg/dL). Chest and abdominal X-rays were unremarkable.
An urgent abdominal CT scan with contrast revealed patchy hypodense areas in the right kidney consistent
with renal infarction (fig. 1). The patient was admitted to the nephrology department, where anticoagulation
with low molecular weight heparin at therapeutic doses was started. Subsequent measurements of vitamin B12,
folate, antinuclear and antiphospholipid antibodies, tumor markers, and lipid metabolism were all normal.
Diagnosis of mutation in the FII 20210 gene (heterozygous) and the MTHFR gene (homozygous) was
confirmed, with homocysteine levels in the upper normal range. The thrombophilia study was otherwise normal. A 99m-Tc-DTPA perfusion study showed a triangular uptake defect in the upper pole of the right kidney consistent with renal infarction. A 99-Tc-DMSA renal scan confirmed diagnosis.
Patient had a favorable course, with disappearance of pain and gradual decrease in LDH. Heparin was
replaced by acenocoumarol for an indefinite time, and folic acid was added due to the finding of homocysteine levels in the upper normal range.
Rapid diagnosis of renal infarction is critical if thrombolysis or surgery is to be attempted to preserve kidney
function. There are several helpful tests for diagnosis, and the choice depends on test availability. CT with
a contrast agent provides a fast, accurate diagnosis. Isotope flow imaging with DTPA-Tc99m shows an absent or decreased perfusion in the affected kidney. Doppler ultrasound has a limited value, and renal arteriography is the definitive diagnostic procedure.
Mutation in the FII 20210 gene is associated to a 30% increase in baseline prothrombin levels that predisposes to thrombotic events. Hyperhomocysteinemia may be congenital or acquired. Acquired forms are secondary to folate or vitamin B12 or B6 deficiency. Congenital forms are due to mutations in the cystathionine-b-synthetase gene or the MTHFR gene, more common, and which is associated to hyperhomocysteinemia particularly in homozygotes with folate deficiency. Hyperhomocysteinemia predisposes to thrombotic events by endothelial activation, muscle cell proliferation, and changes in NO production or sterol metabolism in endothelium.3
Absence of hyperhomocysteinemia in this patient with MTHFR mutation was possibly due to the fact that he was
never detected vitamin B12 or B6 or folate deficiency.
Thrombophilia should be searched in patients with recurrent venous thrombotic events. However, such search
does not appear to be indicated in patients with isolated arterial thrombosis, especially if they have risk factors for arterial disease.
The risk of venous thrombosis in patients with FII 20210 or MTHFR mutation is low. Its role in arterial thrombosis is unclear, with a slight risk of AMI or stroke occurrence. An increased risk exists in patients aged < 55 years and
female patients, with a more significant effect if concomitant coagulation disorders and associated cardiovascular risk factors exist.4
As to therapeutic management, prophylaxis should be started in asymptomatic patients or patients with thrombosis associated to risk situations, and indefinite anticoagulation should be given to patients with
two or more spontaneous thromboses, life-threatening thrombosis, or thrombosis linked to more than one genetic
abnormality.
In our case, the patient was <55 years, and had FII 20210 and MTHFR mutations and cardiovascular risk factors (HBP, former smoker, drinker). Management would have required the previous start of indefinite anticoagulation that would have prevented the occurrence of a third thrombotic event.5
The interest of the reported case lies in the occurrence of renal infarction in a patient with mutation in the FII 20210
and MTHFR genes, a previously unreported clinical condition.