Possible Role of Bone γ-Carboxyglutamic Acid-Containing Protein in the Pathogenesis of Vitamin K Deficiency in Early Infancy

Abstract

In order to investigate the pathogenesis of vitamin K deficiency in early infancy, we measured urinary γ-carboxyglutamic acid (Gla) by high performance liquid chromatography, plasma and urinary bone Gla-containing protein (BGP) by radioimmunoassay, and vitamin K-dependent coagulation activity by Normotest, in newborn and 1-3-month-old infants. The infants were divided into two groups, one of which received vitamin K orally at birth and at the 7th day thereafter, and the other, which did not receive vitamin K, was taken as the control. Urinary Gla level in the control group was fairly steady during early infancy, whereas in the vitamin K-administered group urinary Gla increased with age and was significantly higher than that of the control group from the neonatal period to 1 month of age. The difference in urinary Gla level between the two groups was maximum at 1 month of age. Coagulation activity in both groups increased with age and the activity in the vitamin K-administered group was slightly higher than that in the control, however, the slopes for age versus coagulation activity between the two groups were not significantly different. Plasma BGP level in the control group increased linearly during the neonatal period and then significantly decreased at 1 month of age. The urinary BGP level in the control group increased linearly from the neonatal period to 3 months of age. On the other hand, the plasma BGP level in the vitamin K-administered group was significantly lower compared with that in the control group from 2 days of age to 1 month, and the urinary BGP level was also lower than in the control during the neonatal period but higher than in the control at 1 month of age. Urinary Gla mostly increased at 1 month of age when vitamin K was administered, indicating that there are newly synthesized non-γ-carboxylated, vitamin K-dependent proteins which are changed to the γ-carboxylated form and excreted in urine as free Gla by vitamin K administration, especially at 1 month. The decreased BGP level at 1 month of age in the control group suggests that BGP in plasma deposits to bone, because there is no significant change detected in urinary BGP and Gla. Moreover, the high urinary BGP level at 1 month of age in the vitamin K-administered group suggests that excessive BGP, which is formed as the result of increased bone turnover at 1 month, is the source of this high urinary level. Therefore it is speculated that increased BGP turnover to regulate mineralization at 1 month of age, and induce acceleration of vitamin K requirement of the body and consequently infants easily manifest vitamin K deficiency if there are risk factors decreasing vitamin K intake.