OOA (Old Order Amish)

Inheritance: X-linked
Genes: factor IX

Christmas Disease
Factor IX deficiency
Plasma thromboplastin component (PTC)

Hemophilia
Factor IX
Bleeding

Hemophilia B – Factor IX Deficiency (Christmas disease)

Clinical Characteristics

General description (for patients): 

Hemophilia B is the second most common type of hemophilia.  The eponym comes from the surname ‘Christmas’ of a 5 year-old boy who was reported in the Christmas issue of the British Medical Journal in 1952.  There are three different levels of hemophilia: mild, moderate and severe.  Bleeding is the main sign and may occur anywhere but the most serious consequences follow when the joints and brain are involved.  Involved joints may become chronically inflamed resulting in severe damage with time.  Mild cases may go unnoticed until later on in life, when they occur in response to surgery or trauma.  Internal bleeding may occur anywhere, and bleeding into joints and associated pain and swelling are common. Other symptoms include blood in urine or stool, bruising, nosebleeds, spontaneous bleeding, and prolonged bleeding from cuts, tooth extraction and surgery.  Risk factors are a family history of bleeding and being male.

Medical description:  

This condition is a congenital disorder of blood coagulation caused by a defect in the blood plasma protein factor IX that affects the clotting property of blood.  Abnormal bleeding following relatively minor trauma or following dental surgery should arouse suspicion.  Intracranial bleeding can lead to serious neurological deficits.   Recurrent bleeding into joints can lead to chronic synovitis resulting in eventual destruction.  Early symptoms are pain on motion with limited range of motion following minor bruising.  Diagnosis is confirmed by a prolonged prothrombin time. 

Genetics:

The disorder is caused by a defect in factor IX (plasma thromboplastin component), coded by an X-linked recessive gene.  Thus the vast majority of affected individuals are males although rare females have been reported.  In an endogamous population, however, there is an increased chance that affected males will marry heterozygous females in which case there is a risk that half the female offspring will be affected homozygotes.  The gene locus is at q27.1-27.2.  More than 1500 different mutations have been found in this gene. Factor IX deficiency occurs with considerable frequency among the Amish of Holmes County, OH as well as in other areas secondary to a C>T transition at base 31008 in most individuals. 

Treatment:

The standard treatment currently is infusion of factor IX concentrates to replace the defective clotting factor with amounts dependent upon the severity of bleeding, the site of bleeding and the size of the patient.  To prevent a bleeding crisis, individuals with hemophilia and their families can be taught to administer factor IX concentrates at home at the first signs of bleeding. However people with severe forms of the disease may need ongoing, preventative infusions.  Depending on the severity of the disease, factor IX concentrate may be given prior to dental extractions and surgery to prevent bleeding. 

Prognosis:

The outcome is usually good with treatment.  Most people with hemophilia are able to lead relatively normal lives. However a small percentage of people develop inhibitors of factor IX, and may die from blood loss. 

Ancillary treatments and support:

Due to an increased risk of developing hepatitis through to exposure to blood products, Hepatitis B vaccine is sometimes considered prior to transfusion.  Infusions could also be useful prior to major dental and other surgery.  Affected individuals should be cautioned against contact sports and advised to limit activities with significant risk of trauma. 

Specialists and specialty centers:

Haematologist, internist, orthopedist.

References:

Ketterling, R.P., Bottema, C.D..K., Koeberl, D.D., Li, S., Sommer, S.S.:  T-296-to-M, a common mutation causing mild hemophilia B in  the Amish and others: founder effect, variability in factor IX activity assays, and rapid carrier detection.  Hum. Genet. 87: 333-337, 1991.  PubMed: 1864609

Resources:

National Hemophilia Foundation

Associated Graphics