Field of Science

(Merry) Christmas Disease
So I was feeling a little lazy and thought I should find a disease related to Christmas, that way it’d be topical and I’d look like a genius. Well maybe not a genius, as all I did was type “Christmas” and “disease” into google and it returned “Christmas disease”. Don’t worry though, the disease itself is pretty cool!
Contrary to popular belief Christmas disease is not limited to public drunkenness

Unfortunately for me my attempt at topical blogging reveals that Christmas disease is not named after the holiday but instead after Mr Stephen Christmas, a British migrant  who immigrated to Canada, who was diagnosed at the age of 2 in 1949 with haemophilia. On a return visit to England in 1952 Stephen was again hospitalised and a sample of his blood was sent away to the Oxford Haemophilia Centre where it was determined by Rosemary Biggs and R.G. McFarlane that Mr. Christmas did not have a normal case of haemophilia, he had something that had never been described before.

Haemophilia is best described as a blood clotting disease. All haemophilia cases are genetic and are inherited from your parents and although there are many types the risk is that any blood vessel breakage could result in 'bleeding out' as suffers are unable to clot or coagulate normally so the blood keeps spilling.

The proteins responsible for allowing the blood to clot are called 'Factors' and there are 3 that are particularly important yet unhelpfully named as Factor VIII, IX and XI.
Oh noes I'm bleeding through my skin! Seriously can anyone see where the actual cut is?
Haemophilia C is caused by a genetic mutation that produces a non-functional Factor XI, a.k.a. plasma thromboplastin antecedent. The gene for Factor XI is carried on chromosome 4, which makes it a recessive autosomal disease. All that means is that there is an equal chance for both males and females to get it and for the full blown disease you need to inherit dodgy copies of the gene from both parents but an intermediate form of the disease can still occur if you receive only one dodgy copy. For this reason it is super rare making up about 1% of all haemophilia cases but in small groups where children are encouraged to marry and have children with others from inside the same group, say for example Ashkenazi Jews where C type Haemophilia affects 8% of the population, the proportyion of type C haemophilia cases goes up.

The genetic mutation for types A and B haemophilia are located on the X chromosome so are classified as X-linked disorders rather than an autosomal disorder like type C. This means the disease is more common, and often more serious, in males. The reason for this disparity is that males only have one X chromosome (remember males are XY at their sex chromosomes) while females have two X’s. One dodgy copy of a gene in an X chromosome in males = disease whereas females can in most cases accommodate one dodgy copy and still be fine.

Type A is the most common form of haemophilia accounting for 80% of all cases and is caused by a mutation destroying the activity of Factor VIII, a.k.a. anti-haemophilic factor. Factor VIII forms a complex with other clotting factors in the presence of high calcium concentration that result in a clotting cascade. For those of you with a bit of biology background you will know that Ca is not present in high concentrations anywhere in the body (except the bone) because it is biologically active and so its presence is a potent signal. Nerves use Ca during signalling, immune cells can follow a Ca gradient and other cells use it to talk to each other. Anyway when the concentration that is free in the blood goes up it indicates blood vessel damage and initiates the clotting cascade through activation of Factor VIII.

Finally we work our way back to Stephen Christmas. When the scientists at the Oxford Haemophilia Centre looked they found levels of Factor VIII  was fine (at this stage type C hadn't been discovered so Factor XI wasn't analysed) but Stephen was lacking Factor IX. This type of Haemophilia was classed type B.

Type B haemophilia is X-linked and here the mutation breaks Factor IX, a.k.a. Christmas Factor, that acts as a serine protease. The activity of Factor IX is controlled by either XI or VIII as either can cut Factor IX in half which converts it from an inactive to active form. The cut or cleaved form of Factor IX also requires high Ca to function and in the right conditions will promote coagulation. Stephen Christmas’ condition was treated using transfusions of normal blood which contained normal Factor IX allowing him to clot normally but repeated transfusions in the early 60’s and 70’s resulted in him eventually contracting Human Immuno-deficiency Virus (HIV) which later developed into Auto Immune-deficiency Syndrome (AIDS) which he succumbed to in 1993.

Following the detection of HIV in Stephen’s body he became an active worker and proponent for screen of donated blood to increase the safety of transfusions, which was eventually adopted by 1985.
Stephen Christmas was kept alive by transfusions and I implore you to give blood too. Click here for your closest Australian donation centre and just Google for other countries. Best. Gift. Ever.
While Stephen Christmas’ life may have been afflicted by a horrible disease his gift was to help bring in an era of change that has undoubtedly saved millions of lives by screening donor blood for harmful elements, including HIV Hepatitis B and C viruses amongst many others.

Fun facts!!!
Christmas Disease is cause for a deficiency in functional Factor IX resulting in an inability to clot. Over production of Factor IX can be just as bad though and has in fact been linked to conditions such as deep vein thrombosis which are characterised by inappropriate and unnecessary clotting.

And with that I say have a great holiday period for those of you who are celebrating one and I will be back in the new year after taking a short break to socialise with others in meat-space. Have a good, fun and most importantly safe time and I’ll see you again real soon.

James out.

Rogaev EI, Grigorenko AP, Faskhutdinova G, Kittler EL, & Moliaka YK (2009). Genotype analysis identifies the cause of the "royal disease". Science (New York, N.Y.), 326 (5954) PMID: 19815722
BIGGS R, DOUGLAS AS, MACFARLANE RG, DACIE JV, PITNEY WR, & MERSKEY (1952). Christmas disease: a condition previously mistaken for haemophilia. British medical journal, 2 (4799), 1378-82 PMID: 12997790

1 comment:

  1. Thank you for a little more of the same we CD victims read from one site to another. It's sad at best when you carry a disease few doctors themselves know anything about. We are presently preparing a website,, and it is from here you will be able to read firsthand what we suffer with. CD is a blood disease, and blood effects 100% of the body. At 55 I personally thought there are worse things than CD, and there are, however, at 65 I am beginning to believe it may very well be my death.


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