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Fell Pony
Foal Immunodeficiency Syndrome
Related conditions: anaemia, immunodeficiency
Related terms: Fell pony immunodeficiency; fell pony syndrome; FIS; B-cell lymphopenia
Outline: Foal immunodeficiency syndrome is an inherited autosomal recessive condition that causes fatal anaemia and a compromised immune system in Fell ponies. Affected foals have abnormally low levels of both red blood cells (erythrocytes) and the white blood cell - B lymphocytes (essential for the normal functioning of the immune system). Affected foals become progressively anaemic and are more susceptible to opportunistic infections. There is no curative treatment and all foals die or are euthanased before 4 months of age.
Summary of Information
(for more information click on the links below)
1. Brief description
Foal immunodeficiency syndrome is a fatal condition characterised by abnormally low levels of both red blood cells (erythrocytes) and the white blood cell - B lymphocytes. Erythrocytes and B lymphocytes are formed during foetal development, but their numbers are lower in affected than in unaffected animals, and their levels are not sustained after birth. This is because the normal function of the stem cells, which produce these blood cells, in the bone marrow of affected animals is impaired. As levels of these blood cells drop, affected foals become progressively more anaemic, and are more susceptible to opportunistic infections.
2. Intensity of welfare impact
Affected foals become progressively, and increasingly severely, anaemic and lethargic. The clinical signs include weakness, inactivity, poor growth, breathlessness, reduced appetite, diarrhoea and pale gums. They may also suffer from infections that have an impact on their welfare.
Treatment is usually supportive (palliative), eg through the use of antibiotics to treat secondary infections - and this may prolong life, but affected animals invariably have a severely shortened lifespan.
3. Duration of welfare impact
The prognosis for affected foals is poor, and whilst treatments may reduce clinical signs, all affected horses die or are euthanased before 16 weeks of age.
4. Number of animals affected
Foal immunodeficiency syndrome affects both males and females of the Fell pony breed.
One study found that the prevalence of heterozygous carriers of the condition was as high as 50% in Fell pony adults screened for the defective gene that caused the condition in 2013 - ie they showed no sign of the disease themselves but possessed one copy of the defective gene which they can pass on to any offspring (Carter et al 2013).
5. Diagnosis
The diagnosis is often made post-mortem, but the clinical signs and the fact that Fell ponies have a breed predisposition may be suggestive of the condition in young foals. The most definitive diagnostic test for foal immunodeficiency syndrome is DNA testing to identify for the genetic mutation responsible for the condition.
6. Genetic
The Fell pony breed has a small effective breeding population and has suffered genetic bottlenecks so that the population is genetically very similar. This has likely encouraged the genetic mutation that causes the condition to become more prevalent in this breed.
Foal immunodeficiency syndrome is an autosomal recessive trait in Fell ponies. Horses that inherit two copies of the defective gene, one from each parent (homozygous), will be clinically affected by the condition. If a horse only has one copy of the mutation, inherited from one parent, it will not be clinically affected by immunodeficiency but it will be a genetic carrier (heterozygous) and will pass on the mutated gene to some of its offspring. If two heterozygous horses, each carrying one copy of the mutated gene, are mated together, there is a 25% chance for each of their offspring of being clinically affected with immunodeficiency (ie homozygous) and a further 50% chance of being a heterozygous carrier of the condition.
7. How do you know if an animal is a carrier or likely to become affected?
A DNA test can detect the genetic mutation responsible for foal immunodeficiency syndrome in Fell ponies. The test can identify homozygous affected horses (those with two copies of the mutation) and heterozygous carriers (those with only one copy of the mutation), as well as non-affected horses (with no gene mutation).
8. Methods and prospects for elimination of the problem
Genetic testing for carriers of the foal immunodeficiency syndrome has been available in the United Kingdom since 2010, and the number of adult carriers in Fell ponies is being monitored. Careful breeding management is necessary to decrease the incidence of foal immunodeficiency syndrome. Matings between two carriers should be avoided.
For further details about this condition, please click on the following:
(these link to items down this page)
- Clinical and pathological effects
- Intensity of welfare impact
- Duration of welfare impact
- Number of animals affected
- Diagnosis
- Genetics
- How do you know if an animal is a carrier or likely to become affected?
- Methods and prospects for elimination of the problem
- Acknowledgements
- References
1. Clinical and pathological effects
Foal immunodeficiency syndrome is characterised by abnormally low levels of red blood cells (erythrocytes) and B lymphocytes – a type of white blood cell.
Red blood cells transport over 98% of the oxygen needed by the body, taking up oxygen in the lungs and delivering it, via the circulatory system to body tissues and organs. B lymphocytes are subtypes of white blood cells and have an important role in providing adaptive immunity, which can provide life-long protection against specific pathogens (Tizard 2012). B cells play a large role in the humoral immune response, by responding to foreign antibodies and other proteins found in extracellular fluids. B lymphocytes have receptors on their cell membrane that allow them to bind to a specific “non-self” antigen – molecules such as chemicals, bacteria, viruses or pollen which are foreign to the body. They then initiate the production of antibodies specific to particular pathogens or pathogen-infected cells and which destroy them. Once activated, B cells form memory cells, which “remember” specific pathogens encountered and enable a strong and rapid response if the pathogen is detected again throughout the lifetime of an animal.
Both B lymphocytes and erythrocytes are produced by stem cells in the bone marrow. Horses with foal immunodeficiency syndrome have an inherited genetic mutation that affects the normal production and function of B lymphocytes and erythrocytes. Affected foals may be born with erythroid precursors in the bone marrow, (ie cells that will further differentiate and go on to form red blood cells), levels of circulating B lymphocytes and an erythrocyte cell volume in the blood within the normal range of unaffected foals (albeit in the low range), which suggests functional but limited haematopoiesis (formation of blood cellular components) during foetal development (Tallmadge et al 2012). However, after birth, affected foals exhibit progressively reducing levels of B lymphocytes and red blood cells (anaemia).
Affected horses fail to produce immunoglobulins for antigen-specific immune responses, and as a result are more susceptible to opportunistic bacterial, viral and parasitic infections and are less able to recover from infections than unaffected individuals (Thomas et al 2010). Infections caused by cryptosporidia and adenovirus are particularly common (Tallmadge et al 2012).
In the bone marrow of affected foals, there is evidence of initial abnormal erythroid proliferation (increased levels of abnormal red blood cells - hyperplasia with dysplasia) followed by a rapid and progressive reduction in erythrocyte generation, leading to aplasia where the bone marrow ceases to produce red blood cells (Tallmadge et al 2012). Affected foals may also have smaller than normal lymphoid organs (Thomas et al 2003) and exhibit severe, and progressive anaemia.
2. Intensity of welfare impact
Affected foals appear normal at birth but become progressively and severely anaemic and lethargic. Clinical signs include weakness, increasing breathlessness that causes distress (dyspnoea), listlessness and inactivity (Scholes et al 1998, Tallmadge et al 2012). Affected foals may also show poor growth, reduced appetite, diarrhoea and pale gums. The intensity of the welfare impact of this syndrome is also dependent upon the type, frequency and severity of any infection.
Treatment is usually supportive (palliative), eg through the use of antibiotics to treat secondary infections - and this may prolong life, but affected animals invariably have a severely shortened lifespan.
3. Duration of welfare impact
Antibodies from the mother are transferred to the new born foal through colostrum, a type of milk produced by the mare for the first 2-3 days after birth that is rich in immunoglobulins, which the foal then absorbs through the gut. This protection means that affected foals are therefore clinically normal at birth because they have a functioning passive immune system, at birth. The age of onset of clinical signs of the disease depends on the environmental challenges faced by the foal – eg the number of pathogens it is exposed to in its environment - and the adequacy of passive transfer of immunity from their mother. Usually, horses with foal immunodeficiency syndrome become susceptible to infections from 2 to 6 weeks after birth.
The prognosis for affected foals is poor, and whilst treatments may reduce symptoms, all affected horses die or are euthanased before 16 weeks of age (Tallmadge et al 2012).
4. Number of animals affected
Foal immunodeficiency syndrome affects both males and females equally, and has been reported in the United Kingdom (Scholes et al 1998), United States (1 case: Gardner et al 2006) and the Netherlands (6 cases: Butler et al 2006).
Using anonymous results of DNA testing in the United Kingdom, it was found that 58 of 142 Fell pony foals (41%) were heterozygous carriers for the condition – ie they showed no sign of the disease themselves but possessed one copy of the defective gene which they can on to any offspring. and 12 (8%) were homozygous affected in 2010 (Carter et al 2013). In 2012, of 71 foals tested, 38 (54%) were heterozygous carriers and only 1 was homozygous affected. Of 106 adult Fell ponies tested in 2012, 46 (43%) were heterozygous carriers for the condition (Carter et al 2013).
5. Diagnosis
The clinical signs of anaemia and recurrent infections, and the fact that Fell ponies have a breed predisposition may be suggestive of foal immunodeficiency syndrome, but the diagnosis is often made post-mortem (Thomas et al 2003).
The most definitive diagnostic test for foal immunodeficiency syndrome is the gene probe which detects the mutation responsible (ie DNA testing).
6. Genetics
The Fell pony breed has a small effective breeding population and has suffered genetic bottlenecks resulting in a loss of genetic diversity in the breed and a population. This has likely caused the genetic mutation that causes the condition to become more prevalent in this breed.
Foal immunodeficiency syndrome is caused by a mutation in the sodium/myo-inositol cotransporter gene (SLC5A3; Fox-Clipsham et al 2011). This gene plays a crucial role in the regulatory response to osmotic stress (sudden changes in the solute concentration around a cell) that is essential in many tissues including lymphoid tissues and especially during early embryonic development. It is hypothesised that the genetic mutation alters the function of SLC5A3, leading to a failure to generate red blood cells and lymphocytes. The transition between foetal/neonatal and adult-like haematopoiesis (formation of blood cells) may be an important aspect of the pathogenesis of this condition (Tallmadge et al 2012).
Foal immunodeficiency syndrome is an autosomal recessive trait in Fell ponies. Horses that inherit two copies of the defective gene, one from each parent (homozygous), will be clinically affected by the condition. If a horse only has one copy of the mutation, inherited from one parent, it will not be affected by immunodeficiency but it will be a genetic carrier (heterozygous) and will pass on the mutated gene to some of its offspring. If two heterozygous horses, each carrying one copy of the mutated gene, are mated together, there is a 25% chance of their offspring being clinically affected with immunodeficiency (ie homozygous) and a further 50% chance of heterozygous carriers of the condition.
7. How do you know if an animal is a carrier or likely to become affected?
A DNA test to detect the genetic mutation responsible for fell pony immunodeficiency became available in 2010 in the United Kingdom. The test can be done using blood samples, or non-invasively, using saliva or hairs with roots. It can detect homozygous affected horses (those with two copies of the mutation) and heterozygous carriers (those with only one copy of the mutation), as well as non-affected horses (with no gene mutation).
8. Methods and prospects for elimination of the problem
Genetic testing for carriers of the foal immunodeficiency syndrome has been available in the United Kingdom since 2010, and the number of adult carriers in Fell ponies has reduced over time, from 49% in 2010 (275 of 565 horses tested) to 43% in 2012 (46 of 106 horses tested; Carter et al 2013).
The Fell pony population is small and individuals are registered by the Rare Breeds Survival Trust. Careful breeding management is necessary to decrease the incidence of foal immunodeficiency syndrome. Matings of two carriers should be avoided, since this pairing will lead to 25% of the offspring being affected, and 50% being carriers. Due to the small effective breeding population, it may be necessary to breed carrier horses with normal horses (no genetic mutation), but this paring will still produce 50% carrier offspring, which should then be monitored for future matings.
9. Acknowledgements
UFAW thanks Dr Emma Buckland (BSc PhD), Dr David Brodbelt (MA VetMB PhD DVA DipECVAA MRCVS) and Dr Dan O’Neill (MVB BSc MSc PhD MRCVS) for their work in compiling this section.
10. References
Butler CM, Westermann CM, Koeman JP and Sloet van Oldruitenborgh-Oosterbaan MM (2006) The Fell pony immunodeficiency syndrome also occurs in the Netherlands: a review and six cases. Tijdschrift Voor Diergeneeskunde 131: 114–8
Carter SD, Fox-Clipsham LY, Christley R and Swinburne J (2013) Foal immunodeficiency syndrome: carrier testing has markedly reduced disease incidence. The Veterinary Record 172: 398
Fox-Clipsham LY, Carter SD, Goodhead I, Hall N, Knottenbelt DC, May PDF, Ollier WE and Swinburne JE (2011) Identification of a mutation associated with fatal Foal Immunodeficiency Syndrome in the Fell and Dales pony. PLoS genetics 7: e1002133
Gardner RB, Hart KA, Stokol T, Divers TJ and Flaminio MJBF (2006) Fell Pony Syndrome in a Pony in North America. Journal of Veterinary Internal Medicine 20: 198–203
Scholes SF, Holliman A, May PD and Holmes MA (1998) A syndrome of anaemia, immunodeficiency and peripheral ganglionopathy in Fell pony foals. The Veterinary Record 142: 128–34
Tallmadge RL, Stokol T, Gould-Earley MJ, Earley E, Secor EJ, Matychak MB and Felippe MJB (2012) Fell Pony syndrome: characterization of developmental hematopoiesis failure and associated gene expression profiles. Clinical and Vaccine Immunology 19: 1054–64
Thomas GW, Bell SC and Carter SD (2010) Immunoglobulin and peripheral B-lymphocyte concentrations in Fell pony foal syndrome. Equine Veterinary Journal 37: 48–52
Thomas GW, Bell SC, Phythian C, Taylor P, Knottenbelt DC and Carter SD (2003) Aid to the antemortem diagnosis of Fell pony foal syndrome by the analysis of B lymphocytes. Veterinary Record 152: 618–621
Tizard IR (2012) Veterinary Immunology, 9th edition. Saunders Elsevier, Missouri
© UFAW 2016
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