Foal Immunodeficiency Syndrome (FIS)

Foal Immunodeficiency Syndrome (FIS) is a hereditary disease affecting closely related breeds such as the Fell Pony, Dales Pony and their crosses, e.g. Gypsy Cob/Tinker. The populations of these breeds underwent a significant bottleneck during the last century. A small number of individuals, low genetic diversity and inbreeding contributed to the emergence of a harmful mutation causing FIS.

Foals appear healthy at birth, with no signs of disease. The first clinical signs develop between 2 and 6 weeks of age. The disease is characterized by a markedly reduced number of B lymphocytes and red blood cells and a low concentration of immunoglobulins. Foals therefore have insufficient adaptive immune protection against bacterial, viral and parasitic infections.

The resulting immunodeficiency progressively worsens as the level of immunoglobulins received from the mare's milk declines. The decrease in maternal antibodies corresponds to the period when the first clinical signs appear. Progressive anaemia gradually develops, and affected individuals suffer from weakness, shortness of breath, coughing, diarrhoea and nasal discharge. Growth is slowed, and the condition is accompanied by loss of appetite and often an inability to suckle. The disease is fatal. The foal dies or must be euthanized at 1–3 months of age.

The disease is caused by a mutation in the SLC5A3 gene (g.31894278C>T). The mutation alters the activity of the SLC5A3 gene and can lead to a partial loss of its function, negatively affecting the development of B lymphocytes and red blood cells.

Foal Immunodeficiency Syndrome (FIS) is an autosomal recessive hereditary disease. The disease therefore occurs in individuals that inherit the mutated gene from both parents. These individuals are designated P/P (positive/positive). Carriers of the mutated gene, designated N/P (negative/positive), have inherited the mutated gene from only one parent and show no clinical signs. However, they can pass the disease-causing mutation on to their offspring.

When two heterozygous carriers (N/P) are mated, theoretically 25% of the offspring will be healthy, 50% will be carriers and 25% will inherit the mutated gene from both parents and be affected by FIS. Crossing a healthy individual (N/N) with a carrier (N/P) theoretically produces 50% carriers and 50% healthy individuals. If a carrier (N/P) is mated with an affected individual (P/P), theoretically 50% of the offspring will be affected and 50% will be carriers.

Fox‐Clipsham, L.; Swinburne, J. E.; Papoula‐Pereira, R. I.; Blunden, A. S.; Malalana, F.; Knottenbelt, D. C.; Carter, S. D. Immunodeficiency/Anaemia Syndrome in a Dales Pony. Veterinary Record 2009, 165 (10), 289–290. https://doi.org/10.1136/vr.165.10.289.

Fox-Clipsham LY, Carter SD, Goodhead I, Hall N, Knottenbelt DC, et al. (2011) Identification of a Mutation Associated with Fatal Foal Immunodeficiency Syndrome in the Fell and Dales Pony. PLoS Genet 7(7): e1002133. doi:10.1371/journal.pgen.1002133