Immunology: immunodeficiency - Fell pony syndrome in Horses (Equis) | Vetlexicon
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Immunology: immunodeficiency – Fell pony syndrome

ISSN 2398-2977


Introduction

  • Cause: autosomal recessive inheritance; genetic defect resulting in a mutation in the sodium/myo-inositol cotransporter gene (SLC5A3) on chromosome 26   →    immunodeficiency.
  • Signs: foals <2 months old; insidious onset lethargy, weight loss, opportunistic infections; anemia; diarrhea, nasal discharge and cough are common.
  • Diagnosis: clinical pathology.
  • Treatment: supportive only.
  • Prognosis: hopeless.

Presenting signs

  • Very young foal - foals initially presented at 2-6 weeks. Treated foals may be up to 12-14 weeks old before succumbing.
  • Lethargy   Immunology: Fell pony immunodeficiency syndrome 01    Immunology: Fell pony immunodeficiency syndrome 02  .
  • Weight loss   Immunology: Fell pony immunodeficiency syndrome 06  .
  • Failure to thrive (poor growth)   Immunology: Fell pony immunodeficiency syndrome 06  .
  • Fungal infection of mouth with diphtheritic tongue surface   Tongue: pseudomembranous diphtheritic membrane  .
  • Profound anemia   Oral mucosa: pallor 02    Conjunctiva: pallor 02 - Fell pony immunodeficiency syndrome  .
  • Multiple system, opportunistic infections.

Geographic incidence

  • Worldwide in Fell ponies   Fell Pony  .
  • Most cases are centered on major breeding regions of Cumbria, UK.
  • Case also reported in a Dales pony   Dales Pony  .

Age predisposition

  • 2-3 weeks at first presentation but signs are insidious and probably start around birth.

Breed/Species predisposition

Cost considerations

  • Treatment of opportunistic infections and supportive therapy until death or euthanasia.
  • Mortality rates in some herds up to 25%.

Pathogenesis

Etiology

  • Single point mutation on chromosome 26 resulting in a mutation in the sodium/myo-inositol contransporter gene (SLC5A3).
  • Inherited as recessive mutation.

Predisposing factors

General
  • Dam or sire with history of producing affected offspring.

Specific

  • Breed.

Pathophysiology

  • Suspected bone marrow stem cell anomaly   →   :
    • Immunodeficiency   →   opportunistic infections.
    • Anemia.
    • Thymic/lymphoid hypoplasia.

Timecourse

  • 8-10 weeks maximum.

Diagnosis

Presenting problems

  • Failure to thrive   Immunology: Fell pony immunodeficiency syndrome 06  .
  • Anemia   Oral mucosa: pallor 02    Conjunctiva: pallor 02 - Fell pony immunodeficiency syndrome  .
  • Cough   Coughing  .
  • Diarrhea   Immunology: Fell pony immunodeficiency syndrome 03    Immunology: Fell pony immunodeficiency syndrome 04  .
  • Skin infections, including fungal infections of the mouth   Tongue: pseudomembranous diphtheritic membrane  .

Client history

  • Normal at birth with normal passive transfer of immunity.
  • Onset of failure to suckle, lethargy, ill-thrift or other clinical illness, at about 7-14 days.
  • Or, weak from birth.

Clinical signs

  • Anemia   Oral mucosa: pallor 02    Conjunctiva: pallor 02 - Fell pony immunodeficiency syndrome  .
  • Pale mucous membranes   Oral mucosa: pallor 01    Oral mucosa: pallor 02  .
  • Cough (soft).
  • Purulent nasal discharge   Nose: nasal discharge    Paranasal sinus: sinusitis 03 - nasal discharge    Nose: discharge 07 - purulent (Fell pony immunodeficiency syndrome)  .
  • Halitosis.
  • Oral pseudomembrane - furry plaque on tongue   Candidiasis    Tongue: pseudomembranous diphtheritic membrane  due to candida infection   Candida albicans  .
  • Dysenteric diarrhea   Diarrhea: box  stable    Diarrhea: walls  stable    Immunology: Fell pony immunodeficiency syndrome 03    Immunology: Fell pony immunodeficiency syndrome 04  .
  • Ectoparasitism   Pediculosis: lice    Dermatitis: chorioptic mange 01    Tail: alopecia - psoroptic mange    Sarcoptes scabiei  .
  • Opportunistic infections of respiratory, gastrointestinal systems and skin, eg:
  • Dry coat in poor condition, often russet in color   Immunology: Fell pony immunodeficiency syndrome 06    Immunology: Fell pony immunodeficiency syndrome 05  .

Diagnostic investigation

Hematology Biochemistry
  • Reflecting secondary disease.
Serology Bone marrow aspirate
  • Small numbers of erythroid precursors.

Confirmation of diagnosis

Discriminatory diagnostic features

  • Breed and history.
  • Signs.

Definitive diagnostic features

  • Hematology and pathology (lymph node biopsy).
  • DNS test to identify genetic mutation at the Animal Health Trust, UK.

Gross autopsy findings

  • Pale, uniformly pink inactive bone marrow   Bone marrow: Fell pony immunodeficiency syndrome - pathology  .
  • Small thymus   Thymus: pleural inflammation - pathology  .
  • Small peripheral lymph nodes.
  • Fluid small intestinal contents.
  • Pseudomembranous covering on tongue   Tongue: pseudomembranous diphtheritic membrane  .
  • Multifocal hepatic necrosis.
  • Pneumonia   Lung: pneumonia - pathology  .
  • Intestinal fungal ulcerative colitis   Intestine: ulcerative fungal enterocolitis 01 - pathology    Intestine: ulcerative fungal enterocolitis 02 - pathology  .
  • Infected skin wounds.
  • Pancreatitis.

Histopathology findings

Bone marrow
  • Decreased active marrow.
  • Increased hematopoietic cells and decreased lipocytes.
  • Abundant megakaryocytes and granulocyte series cells.
  • Increased neutrophil precursors.
  • Abundant hemosiderin granules in macrophages.
Lymph nodes
  • Hypoplasia.
  • Decreased numbers of lymphocytes.
  • Absent germinal centers   Lymph node: absent germ centers - histopathology  - compare with normal   Lymph node: normal - histopathology  .
  • Macrophages present, plus neutrophils - being particularly abundant in inflamed nodes.
Thymus
  • Hypoplasia.
  • Small lobules with poor demarcation of cortex from medulla.
  • Prominent epithelial structure.
  • Few lymphocytes.
Spleen
  • Hypoplasia.
  • Contracted red pulp.
  • Numerous siderophages.
  • Absent germinal centers.
  • Few peri-arteriolar lymphocytes.
Intestine
  • Decreased plasma cells in lamina propria.
  • No germinal centers in gut associated lymphoid tissue.
  • +/- cryptosporidia associated with apical enterocytes and villous atrophy.
  • +/- basophilic intranuclear inclusion bodies in enterocytes consistent with adenovirus infection.
Liver
  • Some hemosiderosis of hepatocytes and Kupffer cells.
  • Multifocal hepatic necrosis +/- neutrophil and macrophage response.
Other
  • Bronchitis, bronchiolitis, suppurative bronchopneumonia.
  • Pancreatitis.
  • Multifocal myocardial necrosis.
  • Suppurative cellulitis associated with cutaneous injury.
  • Lingual hyperkeratosis and superficial epithelial colonization with bacteria and yeasts.
  • Sialoadenitis.
  • Neuronal chromatolysis involving trigeminal, cranial mesenteric and peripheral nerve ganglia.

Differential diagnosis

Anemia

Treatment

Standard treatment

Prevention

Group eradication

  • Genetic testing of all breeding animals for mutation.
  • Breed heterozygotes with animals known to be homozygous normal to maintain genetic diversity but eliminate possibility of breeding homozygous affected animal.

Outcomes

Prognosis

  • Hopeless, affected foals typically die by 3 months of age.
  • Highly fatal - few confirmed cases will live.

Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Carter S D, Fox-Clipsham L Y, Christley R & Swinburne J (2013) Foal immunodeficiency syndrome: carrier testing has markedly reduced disease incidence. Vet Rec 172 (15), 398 PubMed.
  • Tallmadge R L et al (2012) Fell pony syndrome: characterisation of developmental hematopoesis failur eand associated gene expression profiles. Clin Vaccine Immunol 19 (7), 1054-1064 PubMed.
  • Fox-Clipsham L Y et al (2011) Identification of a mutation associated with fatal Foal Immunodeficiency Syndrome in the Fell and Dales pony. PLoS Gent (7), e1002133 PubMed.
  • Fox-Clipsham L Y, Brown E E, Carter S D & Swinburne J E (2011) Population screening of endangered horse breeds for the foal immunodeficiency syndrome mutation. Vet Rec 169 (25), 655 PubMed.
  • Fox-Clipsham L et al (2009) Immunodeficiency/anaemia syndrome in a Dales pony. Vet Rec 165 (10), 289-290 PubMed.
  • Gardner R B, Hart K A, Stokol T, Divers T J & Flaminio J B F (2006) Fell Pony Syndrome in a pony in North America. J Vet Intern Med 20 (1), 198-203 PubMed.
  • Thomas G W, Bell S C & Carter S D (2005) Immunoglobulin and peripheral B-lymphocyte concentrations in Fell pony foal syndrome. Equine Vet J 37 (1), 48-52 PubMed.
  • Thomas G W, Bell S C, Phythian C et al (2003) Aid to the antemortem diagnosis of Fell pony foal syndrome by the analysis of B lymphocytes. Vet Rec 152 (20), 618-621 PubMed.
  • Dixon J B et al (2000) Discriminant and multiple regression anelysis of anemia and opportunistic infection in Fell Pony foals. Vet Clin Pathol 29, 84-86 PubMed.
  • Perryman L E (2000) Primary immunodeficiencies of horses. Vet Clin North Am Equine Pract 16(1), 105-116 PubMed.
  • Richards A J M et al (2000) Anemia, diarrhea and opportunistic infections in Fell Ponies. Equine Vet J 32, 386-391 PubMed.
  • Young K M & Lunn D P (2000) Immunodiagnostic testing in horses. Vet Clin North Am Equine Pract 16 (1), 79-103 PubMed.
  • Scholes S F E et al (1998) A syndrome of anemia, immunodeficiency and peripheral ganglionopathy in Fell pony foals. Vet Rec 142, 128-134 PubMed.

Other sources of information

  • Knottenbelt D C (1999) Fell pony syndrome. In: Proc 38th BEVA Congress. pp 71-72.