Prenatal diagnosis of factor 13 deficiency and its recurrence.

A young third gravida was referred with prenatal diagnosis of factor XIII deficiency at 20 weeks of pregnancy for Medical Termination of Pregnancy (MTP). Her first baby, who was born by emergency Lower Segment Caesarean Section (LSCS) for fetal distress, had intracranial haemorrhage in the early neonatal period and was investigated elsewhere and diagnosed to have factor XIII deficiency. The child currently has global developmental delay and cerebral palsy. The mother had a second-degree consanguineous marriage and the couple were diagnosed to be carriers of factor XIII deficiency. She had lot of barriers to get prenatal diagnosis during the second pregnancy and it ended up in Intra Uterine Fetal Death (IUFD) at 27 weeks. During the current pregnancy, prenatal diagnosis (PND) was done only after the second trimester amniocentesis and the genetic mutation was F13 A1, Ex12, C.1687 G>A. Second trimester MTP in a previous scarred uterus was difficult as it is essential to avoid scar rupture. PND during the first trimester is ideal.

Long-term prophylaxis in patients with severe congenital factor XIII deficiency is not complicated by inhibitor formation.

: Congenital factor XIII (FXIII) deficiency is a rare bleeding disorder accompanied by a variety of bleeding events. Severely deficient patients require regular replacement therapy. With development of FXIII concentrate, the risk of viral infections transmitted by fresh frozen plasma and cryoprecipitate is diminished, but the possibility of inhibitor development remains a challenging issue in the management of these patients. The aim of this study was to assess FXIII inhibitor development in Iranian patients with FXIII deficiency (FXIIID). This study enrolled 50 (30 women and 20 men) patients with severe congenital FXIIID from southeast Iran who underwent long-term (more than 4 years or more than 50 injections) prophylaxis with FXIII concentrate (Fibrogammin P, Dade Behring, Marburg, Germany). We evaluated plasma FXIII activity and FXIII inhibitor on day 28 after the last prophylaxis administration. The method for investigation of FXIII inhibitor was based on Bethesda assay. The mean age of the study population was 13.8 ±â€Š8.3 years. The minimum and maximum FXIII activity levels were less than 1-4.5% (mean ±â€ŠSD, 2.6 ±â€Š0.7%). Our investigations showed that all patients with severe form of FXIIID were treated without inciting inhibitor development. Despite long-term prophylaxis in the studied patients, none was found to have developed FXIII inhibitors.

Arg77His and Trp187Arg are the most common mutations causing FXIII deficiency in Iran.

The aim of this study was to review the literature for the genetic mutations causing inherited factoe XIII (FXIII) deficiency in patients from Iran, where the consanguineous marriage is common. Data were collected from 30 patients (18 males and 12 females) with FXIII deficiency, from 26 unrelated families. Data of mutation analysis were obtained from 2 previously published studies. A total of 7 mutations consisting of 5 new mutations and 2 previously reported mutations were identified. Of the 5 novel missense mutations, 2, Arg77His and Trp187Arg, were the most common in Iranian FXIII-deficient patients. In regions like Iran with high rate of consanguineous marriages, the identification of common mutations in disease like severe FXIII deficiency increases the capacity to make a precise screening and diagnosis assays to screen and diagnose families with high risk of FXIII deficiency for prevention of clinical complications in them.