Four factor deficiency.
Four factor deficiency is variably associated with mild to fatal bleeding. We describe a 3-month-old boy, born of consanguineous parents, who presented with a right subdural haematoma and a clotting screen showing a prothrombin time (PT) > 100 s, an activated partial thromboplastin time (aPTT) > 150 s, a fibrinogen of 0.4 g/l, and fibrinogen degradation products < 1 microg/ml. He was given 300 U of factor IX concentrate (containing factors II and X) and 1 mg of vitamin K intravenously. Forty-five minutes later, clotting tests showed a PT of 24 s, an aPTT of 31 s and a fibrinogen of 2.6 g/l. The patient was found to be deficient in all the vitamin K-dependent factors: factors II, VII, IX and X, protein C and protein S. A 14-base deletion was found in intron 1 (bases 1056-1069) of the gamma-carboxylase gene. The patient and his elder sister were homozygous for this deletion, whereas both parents were heterozygous. The deletion destroys a reverse palindromic sequence (TTGAGGCAA) of the type often associated with cis-acting elements. Our results suggest that this element may be involved in the regulation of gamma-carboxylase expression. Expression studies are being completed so that this region can be definitively ascribed as a cis-acting element involved in gene regulation.
Royal Hospital for Sick Children, Edinburgh, UK. angela.thomas@luht.scot.nhs.uk
Angela
A
Thomas
David
D
Stirling
D001779:Blood Coagulation Factors / Q000378:metabolism; D001780:Blood Coagulation Tests; D019735:Carbon-Carbon Ligases / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D003241:Consanguinity; D005168:Factor VII Deficiency / Q000209:etiology; D005171:Factor X Deficiency / Q000209:etiology; D005260:Female; D006408:Hematoma, Subdural / Q000209:etiology; D002836:Hemophilia B / Q000209:etiology; D006801:Humans; D007020:Hypoprothrombinemias / Q000209:etiology; D007223:Infant; D007438:Introns / Q000235:genetics; D008297:Male; D020151:Protein C Deficiency / Q000209:etiology; D011499:Protein Processing, Post-Translational / Q000235:genetics; D018455:Protein S Deficiency / Q000209:etiology; D017384:Sequence Deletion; D019851:Thrombophilia / Q000235:genetics*; D014812:Vitamin K / Q000627:therapeutic use
D001779:Blood Coagulation Factors; D014812:Vitamin K; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase