Genetic Polymorphism of VKORC1-1639 in Children With Intracranial Hemorrhage Due to Vitamin K Deficiency

Abstract

Intracranial hemorrhage due to vitamin K deficiency is a serious disease that can lead to morbidity, mortality, and mental retardation. Our goal in this study is to determine the frequency of VKORC1-1639 G>A polymorphism in patients who have undergone intracranial hemorrhage due to vitamin K deficiency bleeding (VKDB). To study VKORC1-1639 G>A polymorphism, blood was drawn from patients (n = 51, age 8:0 ± 6:5 years) followed at the Pediatric Neurology and Hematology section, Faculty of Medicine, Erciyes University, between 1990 and 2016, diagnosed with VKDB as idiopathic or from patients diagnosed with intracranial hemorrhage due to secondary vitamin K deficiency and also from volunteers (n = 51, age 11 ± 4.5 years). Intensive care and nutrition needs of patients and the laboratory radiological imaging results and treatments that were applied were analyzed through scanning the files of the patients and information received from families. Through detailed physical examination, patients with neurologic sequelae and ongoing epilepsy were determined. The results were compared to clinical and laboratory results with control group. Eight (15.7%) of the patients were normal, 29 (56.9%) heterozygous carrier, and 14 (27.5%) homozygous mutants. In the control group, 19 (37.3%) were normal, 19 (37.3%) heterozygous carriers, and 13 (25.5%) homozygous mutants. The VKOR1-1639>A (SNP:rs9923231) mutant positivity (homozygous plus heterozygous mutant) was significantly higher in the patient group when compared to controls. There were no significant differences between patient and control groups in terms of the prognosis.

Vitamin K Deficiency Bleeding in Infancy

“…Several reports have revealed that genetic factors can influence the vitamin K-dependent coagulation system and intraventricular hemorrhage [14,15]. Further studies regarding the usefulness of testing for genetic variants to prevent and diagnose VKDB are warranted.…”

“…Polymorphisms in VKORC1 (G-1639A) and coagulation factor 7 (F7-323 Ins10) were reportedly associated with intraventricular hemorrhage or low factor VII levels [14]. Recently, the presence of variant alleles in VKORC1 (SNP: rs9923231) was reportedly associated with vitamin K deficiency bleeding (VKDB) [15]. Although reports that suggest a relationship between VKORC1 genetic variants and VKDB in Japan are lacking, the low enzyme activity of vitamin K epoxide reductase might be associated with VKDB in infancy because of the ethnic differences in the incidence of VKDB in infancy.…”

Recurrent Intracranial Bleed in 3 Siblings: Short of a Shot of Vitamin K!

“…Whether these polymorphisms have a functional effect on vitamin Kdependent coagulation factors remains to be seen. 7,[9][10][11] Although the index child did not suffer intracranial bleed, he did require a second dose of parenteral vitamin K at 9 weeks due to deranged coagulogram. Traditional 1 mg intramuscular prophylaxis gives almost complete protection against VKDB.…”

Genetics of Spontaneous Intracerebral Hemorrhage: Risk and Outcome

“… Unal et al (2014) described that a newborn presented with intracranial bleeding had a mutation of T903C in PROC . Other genes related to perinatal and pediatric ICH including VKORC1 (encoding vitamin K epoxide reductase complex subunit 1) ( Berber et al, 2018 ), F10 (encoding FX) ( Herrmann et al, 2005 ), and F13 (encoding FXIII) ( Göpel et al, 2002 ; Table 5 ).…”