PB0567 - Homozygous LMAN1 gene mutation in a 14-year-old girl with combined Factor V(FV) and FVIII (FVIII) deficiency

Background: Combined FV and FVIII deficiency, a rare bleeding disorder with an incidence of 1:1,000,000, is inherited in an autosomal recessive manner. Therefore, it is more common in consanguineous such as Turkey. Mutations in lectin, mannose binding 1(LMAN1) and multiple coagulation factor deficiency 2(MCFD2) are responsible for causing the deficiency.

Aims: to report a second case with combined FV and FVIII deficiency in Thailand

Methods: a case report

Results: A 14-year-old girl presents with excessive bleeding post dental procedure at 9 years of age. At that time, she did not require any blood transfusion. She also has excessive menstruation that lasts 1-2 weeks with 3-4 pads per day used since menarche at 10 years of age. None of the family members has a bleeding tendency. The Thai Pediatric Bleeding Questionnaire is a 5 score. Her investigations demonstrate as follows; Hb 10.2 g/dL, prothrombin time 16.8, aPTT 60 sec, FVIII activity 15.4, vWF Ag 114.2. vWF activity 85%. Her parent blood work demonstrates as follows; mother: PT 11.5, PTT 30.7 sec, and FVIII activity 108.6%, father: PT 10.3, aPTT 28.8 sec, FVIII activity 133.8%. She was previously transfused with cryoprecipitate to prevent bleeding before dental extraction with no excessive bleeding. A whole genome sequencing reveals homozygous c.1366C>T, p.Arg456Ter (pathogenic) in the LMAN1 gene. Subsequently, the FV level was done with the result of 9.7. The first female case with combined FV and FVIII deficiency reported in Thailand has FV 10 and FVIII 12.5%, presenting with excessive bleeding after minor trauma and tooth extraction. WGS shows compound heterozygous c.823-1G>C and c.1366C>T in the LMAN1 gene.

Conclusion(s): This deficiency might cause excessive bleeding related to an invasive procedure, requiring bleeding prevention by using fresh frozen plasma. The c.1366C>T mutation in the LMN1 gene may be a prevalent causative variant for combined FV and FVIII deficiency in Thailand.