Hemophilia A (H8-related)

Gene: H8

Transmission: Sex linked, recessive

For an X-linked recessive genetic disease, a male must have one copy of the mutation in question to be at risk of developing the disease.  All affected males transmit the mutation to all the females of their offspring. A female must have two copies of the mutation in question to be at risk of developing the disease. Females with only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Substitution, H8 gene (splicing error): c.6073+2 A>G, intron19, Chr.X

Medical system: Blood (coagulopathy)

Breed: Domestic Cat shorthair

Age of onset of symptoms: Following trauma or surgery, susceptible from birth.

Haemophilia A is an inherited clotting disorder characterized by a deficiency or absence of factor VIII, which is involved in the intrinsic pathway of secondary blood clotting (hemostasis). The genetic cause of haemophilia A is a mutation in the F8 gene, found on the X chromosome, such that the disease is sex linked. As such, haemophilia A affects predominantly male animals while female animals are predominantly asymptomatic carriers.  The H8 gene is large with up to 26 exons, and multiple mutations have been reported in both humans and dogs as the cause of haemophilia A in these species.

Generally, the first clinical signs of haemophilia A in an animal are hemorrhages occurring after trauma or surgery.  Diagnostic approaches rely on coagulation tests such as ACT, aPTT, PT, and TT, followed by testing for factor VIII activity. Pedigree analysis helps with the diagnosis due to the sex-linked inheritance pattern of the disease.  Treatment of hemophilia A is symptomatic, aiming to stabilize bleeding episodes often via blood transfusions.  Prevention relies primarily on identifying carrier animals including the mothers and possibly female littermates of affected male animals and excluding these animals from breeding programs.

Historically, haemophilia A has been periodically diagnosed in domestic as well as purebred cats, based on clinical signs and laboratory testing.  To date, little molecular characterization of haemophilia A and the F8 gene in cats has occurred.  Recently a single domestic cat presented with lameness and moderate anemia.  Laboratory tests revealed very low Factor VIII activity, and a diagnosis of haemophilia A was made.  Molecular studies identified a mutation within intron 19 of the H8 gene that was likely to be responsible for a splicing error and the resulting clinical signs.  Additional mutations in the F8 genes will most likely be identified in the future as additional cases of feline haemophilia are characterized at the molecular level.

References:

OMIA link: [0437-9685]

Beetz S, Weingart C, Renner A, et al. (2024) [Hemophilia A in a male cat with intermittent lameness]. Tierarztl Prax Ausg K Kleintiere Heimtiere 52:314-323.  [pm/39447565]

Lyons LA. (2024) Genetic testing: practical dos and don’ts for cats.  J Feline medicine and surgery 26:1-13.  [pm/39648935]

Littlewood JD, Evans RJ. (1990) A combined deficiency of Factor-VIII and contact activation defect in a family of cats. British Veterinary Journal 146:30-35.  [pm/2306600]

Cotter SM, Brenner RM, Dodds WJ. (1978) Hemophilia A in three unrelated cats. J Am Vet Med Assoc 172:166-8.  [pm/627514]

With contributions by: Samya Legault and Maxym Mercier, Class of 2030, Faculty of Veterinary Medicine, University of Montreal.  (Translation: DWS).