Combined Factor V and VIII Deficiency with LMAN1 Mutation: A Report of 3 Saudi Siblings

Case series Patients: Male, 7-year-old • Female, 5-year-old • Male, 12-year-old Final Diagnosis: Combined deficiency of FV and FVIII (F5F8D) Symptoms: Bleeding signs and symptoms Medication: — Clinical Procedure: — Specialty: Hematology • Pediatrics and Neonatology OBJECTIVE: Rare disease BACKGROUND: Combined factor V and factor VIII deficiency (F5F8D) is a rare bleeding disorder with an incidence of 1: 1 000 000. The identified mutations were observed in LMAN1 and MCFD2 genes. This case report presents the cases of 3 Saudi siblings with the genetic mutation of LMAN1 causing F5F8D, and highlights the challenges in diagnosis and treatment. CASE REPORTS: Patient X, a 7-year-old boy, was misdiagnosed with hemophilia A after a history of prolonged circumcision bleeding and epistaxis. He was referred to our clinic for pre-operative assessment. Blood workup showed prolonged PT and aPTT, which were normalized by mixing studies. Since his previous diagnosis could not explain a prolonged PT, further investigations were performed, revealing low levels of FVIII and FV. Genetic testing confirmed a c.822G>A homozygous LMAN1 mutation. The other 2 siblings (patient Y and Z), who were 5- and 12-year-old, respectively, girls, were also assessed. They both had a history of epistaxis. The younger sibling also had an episode of bleeding after tooth extraction, and physical examination of this patient revealed a bruise over her left thigh. The older sibling had menorrhagia. Blood workup of both revealed prolonged PT and aPTT, with complete correction by mixing study, and low levels of FV and FVIII. The patients’ backgrounds and lab results were highly suggestive of F5F8D. CONCLUSIONS: This case report describes an extremely rare bleeding disorder. More attention should be directed toward this disease, and a careful evaluation of suspicious cases should be performed to better diagnose and manage these patients.