Congenital Vitamin K-Dependent Clotting Factors Deficiency Type 1: A Rare Bleeding Disorder

Abstract

Combined deficiency of vitamin K-dependent clotting factors is usually an acquired clinical problem, often resulting from liver disease, malabsorption or warfarin overdose. However, an inherited form of the disease is very rare. Here we report a 4-month-old girl who presented with a 2-week history of multiple bruises and a 1-day history of right thigh swelling after receiving her 4th month vaccine. Laboratory investigations showed anemia (Hb 6.0 g/dL) with extremely prolonged PT and APTT. Factor assay revealed deficiency of vitamin K-dependent clotting factors II, VII, IX, X as well as protein C and protein S. Whole-exome sequencing detected a novel homozygous mutation (c.44-5T>A p.(?)) in the γ-glutamyl carboxylase (GGCX) gene responsible for the autosomal recessive combined vitamin K-dependent clotting factors deficiency type 1.

Keywords

• vitamin k
• γ-glutamyl carboxylase
• epoxide reductase complex
• whole-exome sequencing
• hemorrhage, clotting factors