Haemophilia B Leyden in Greece

Abstract

SummaryIn this paper, a five generation Greek family is described with haemophilia B. The disease is characterized by a normal ox-brain prothrombin time, normal levels of the vitamin-K dependent clotting factors VII and X and a proportional reduction of factor IX acttivity and antigen levels all of which is consistent with the cross-reacting material negative form of haemophilia B. However, in this family the factor IX levels in the three patients of generation V are around 1 U/dl while the three older patients in generation III have factor IX levels ranging from 28 to 44 U/dl. In the oldest patient of generation V we observed a rise of the factor IX level from 1 U/dl up to the age of 13 to 10 U/dl at age 14. In addition, the older patients have very mild bleeding symptoms or none at all, while the young ones have occasional spontaneous haemorrhages in muscles and joints, compatible with severe or moderately severe haemophilia. The disease appears to be similar to haemophilia B Leyden which has been described in a Dutch family.

Structural and functional basis of the developmental regulation of human coagulation factor IX gene: factor IX Leyden.

“…Normally, factor IX gene expression increases during the perinatal stage and reaches its subadult level in a few weeks after birth (5-7). The factor IX genes of the hemophilia B Leyden trait, however, do not express until the onset of puberty (8,9). After onset of puberty, the factor IX level in the peripheral blood of patients with this phenotype gradually rises to a subnormal or normal level at a rate of -5% per year.…”

A case of non‐resolving hemophilia B Leyden in a 42‐year‐old male (F9 promoter + 13 A>G)

“…At puberty, and thereafter, it is assumed that testosterone‐dependent transcription, mediated by an FIX promoter androgen response element (ARE) and possibly binding of the D‐site binding protein (DBP) to an upstream sequence, becomes more important [6]. With specific reference to the subject described here, nucleotide substitutions at + 13 have been shown to disrupt C/EBP binding, and in all previous reports have been associated with the amelioration of the phenotype following puberty [7–9]. In general, these reports describe cases with clotting factor activities rising from ∼ 0.03 IU mL −1 to ∼ 0.40 IU mL −1 after puberty, at a rate of ∼ 0.05 IU mL −1 per year.…”

Μοριακοι Δεικτες Παρακολουθησης Της Κληρονομησης Της Αιμορροφιλιας Στην Ελλαδα Και Προσδιορισμος Της Μοριακης Της Αιτιολογιας

“…Ίσως η δημοσίευση της πρώτης βάσης δεδομένων των μεταλλάξεων του γονιδίου του FIX σε ασθενείς από το Ηνωμένο Βασίλειο (Saad et al, 1994) (Briet et el, 1982(Briet et el, , 1985 καταδείχθηκε η σχέση της αύξησης των επιπέδων τεστοστερόνης με την αύξηση των επιπέδων FIX:C στην οικογένεια και χρησιμοποιήθηκε επιτυχώς η χορήγηση τεστοστερόνης για θεραπευτικούς σκοπούς. Η δεύτερη οικογένεια με την ίδια εικόνα βρέθηκε στην Ελλάδα (Mandalaki et al, 1986) και περιλάμβανε 9 ασθενείς σε ένα γενεαλογικό δένδρο 5 γενεών. Σε τρεις από αυτούς, που διαγνώσθηκαν αμέσως μετά τη γέννηση τους, τα επίπεδα FIX:C ήταν μόλις 1% και παρέμειναν τόσο χαμηλά μέχρι την έναρξη της εφηβείας, οπότε και εκτινάχθηκαν στο 10% για να φθάσουν μέχρι και το 45% (που δε συνεπάγεται πλέον νόσο) στα ώριμα άτομα.…”