April 17 is observed as ‘World Haemophilia Day’ since 1989, to commemorate the birthday of Dr Franc Schnabel (1947-2013) from Boston, USA. Haemophilia otherwise known as the ‘Royal Disease’ is an inherited sex-linked X chromosome disorder causing exaggerated bleeding due to deficiency of clotting factors VIII or IX, on the basis of which the disease is classified as Haemophilia A (VIII deficiency) or Haemophilia B (IX deficiency). This disease manifests almost entirely in males.
The sex chromosomes in the female are XX and in the male XY. The haemophilia gene is carried on the X chromosome in both sexes.
If only one X chromosome is affected in the female, the remaining normal X chromosome blocks the expression of clinical manifestations of haemophilia and she would be an asymptomatic ‘carrier’. However in the male (XY), if the X chromosome is affected, there is no normal X chromosome to block the clinical features - (Y has no blocking action) thus resulting in bleeding from any part of the body - a classical ‘Haemophilia’ patient.
There is a rare possibility of a female developing the disease if her father is a ‘haemophiliac’ and the mother a ‘carrier’ (both XX are affected). If a normal female marries a haemophiliac male, all their daughters would be asymptomatic carriers, but none of their sons would be affected. If a ‘carrier’ female marries a normal male, upto 50 per cent of their sons would be ‘haemophiliacs’ and 50 per cent of their daughters would be ‘carriers’. Very rarely due to spontaneous genetic mutations in the X chromosome, one can develop the disease without family history.
The prevalence of Haemophilia A which is four times more common than Haemophilia B is around one in 10,000 live births. In India there are about one lakh haemophilia patients. Haemophilia is described even in the Jewish Holy Book ‘Talmud’ where it is stated that ‘if the first two male children in a family developed excessive bleeding during circumcision, the next son need not be circumcised.’ Rarely the disease can occur by genetic mutation of the X chromosome without a family history.
Queen Victoria propagated ‘Haemophilia’ to various kingdoms in Europe, hence it is called the ‘Royal Disease’ and she was nicknamed as the ‘Founder of Haemophilia in the European Royalty’. She served the longest time in history, 64 years as the British monarch (1837 - 1901). Twenty prime ministers served under her. She was the first and last Empress of India (1876-1901). Victoria, the daughter of Prince Edward (who was the son of King George IV) and Princess Victoria a widowed German Princess, was born on 24 May 1819 and was christened as Alexandrina. She had nine children, (five daughters and four sons). Although the queen was a ‘haemophiliac carrier’ all her deliveries were normal. Her marriage to Prince Albert of Saxe Coburg was held (three years after her coronation as queen) on February, 1840.
Queen Victoria’s first daughter Princess Victoria, born on November 1840 was normal. Her second daughter Princess Alice born in 1841, was a ‘haemophilia’ carrier who got married to Louis IV of Russia. Princess Alice’s daughter, the Empress Alexandra of Russia was married to the last Czar, Alexander Nicholas II. Their youngest son Alexi Romanov (Victoria’s great grandson) born in 1904 was a ‘haemophiliac’. Unfortunately the whole Czar family including the 14 year old Alexi was shot dead by the Russian Revolutionaries in 1918. Using genetic DNA analysis of the bone fragments of the executed Prince Alexi, his sister Anastasia and mother Alexandra, scientists were able to diagnose their disease as ‘Haemophilia B’.
Prince Leopold, Queen Victoria’s eighth child born in 1853 was a ‘haemophiliac’ and died in 1884 after a minor accident, at the age of 31 years. Her last daughter Princess Beatrice born in 1857 was a ‘haemophilia carrier’ who later became the Queen of Spain. Beatrice’s two sons died of ‘haemophilia’ at the age of 19 and 31. Queen Victoria’s carrier state appears to have been due to spontaneous mutation of the genes in view of the obvious absence of any ‘haemophilia’ in her parents’ lineage. Two (out of five) of her daughters were carriers, and one son (out of four), two grandsons and six great grandsons were haemophiliacs. Victoria’s descendents are still the monarchs of countries like Norway, Sweden, Spain and Denmark.
Haemophilia can now be diagnosed early by molecular genetic testing, and even predict it in the new borns by analysing the amniotic fluid of pregnant women. In Kerala, a Haemophiliac Society was started in 1987 and there are branches in almost every city. Fresh blood transfusion which was the earlier form of treatment is not routinely advised now because of the chances of transmission of diseases like AIDS, Hepatitis B and C. Factors VIII/IX manufactured by a recombinant DNA technique is the standard treatment now (available as injection). With this treatment, the life span of a haemophiliac could be prolonged from 11 years to 60 years.
Prof K P Poulose, (Principal Consultant in Medicine, SUT Hospital, Pattom)