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Genetic Welfare Problems of Companion Animals
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Abyssinian
Amyloidosis
Related terms: generalised amyloidosis; renal amyloidosis
VeNom term: Amyloidosis (VeNom code: 383).
Related conditions: chronic renal failure
Outline: Amyloidosis is a condition that occurs when amyloid, a substance of abnormally folded proteins, is deposited in various organs of the body. Amyloids cause damage by displacing normal cells. In Abyssinian cats, amyloids are primarily deposited in the kidneys, which leads to decreased kidney function, and fatal kidney failure can occur. The clinical signs of amyloidosis are related to progressive kidney damage, and include excessive drinking and urination, dehydration, poor coat quality, gingivitis (inflammation of the gums), lethargy, lack of appetite (inappetance) and weight loss.
Commonly, cats develop amyloidosis between 1 and 5 years of age, although the progression of the disease is variable. For some affected cats, the deposition of amyloid may occur slowly, and kidney function may remain adequate for several years. For others, the deposition of amyloid may be rapid and severe, with kidney failure developing within one year. By the time clinical signs are noticeable, and amyloidosis is suspected, there is likely to be significant amyloid deposition and associated kidney damage, and therefore diagnosis is often made on post-mortem examination.
Amyloidosis in cats is rarely reported in the scientific literature, and the mode of inheritance is not known. This may indicate the condition is rare or that it is underreported due to a lack of diagnosis. We do know that Amyloidosis is more prevalent in Abyssinians cats than in most other breeds, and the trait is inherited within families. It is therefore recommended that breeding from affected cats is avoided, and from those with severely affected relatives, including grandparents, siblings, previous offspring and siblings of parents.
Summary of Information
(for more information click on the links below)
1. Brief description
Amyloidosis involves the extracellular deposition of insoluble, fibrous proteins – amyloids – into various tissues of the body. Amyloids are inappropriately folded versions of normal proteins and polypeptides, which have collected together to form insoluble fibrils. A range of different proteins can form an amyloid, but the most common type is derived from serum amyloid A.
In Abyssinian cats, amyloids derived from serum amyloid A are primarily deposited in the kidney, and to a lesser extent, in other tissues such as the spleen, stomach, intestines, thyroid, and heart. These amyloids are more difficult for the body to break down than normal proteins and so build up and displace healthy tissue, disrupting the normal processes of the kidney. Affected kidneys become enlarged, inflamed and unable to function as normal. They are unable to filter the toxic waste products of the body, such as urea, from the blood, and are also unable to reabsorb valuable amino acids and protein back into the body and lose them into the urine.
As the disease progresses, there is more damage to the kidney tissue as it is replaced with amyloid fibrils, and eventually this causes kidney failure which can be fatal. Affected cats may have nonregenerative anaemia, as a result of protein loss from the blood and may show abnormally high levels of nitrogen and phosphate in the blood (azotaemia, hyperphosphataemia). This in turn leads to excessive acidity of the blood (metabolic acidosis), which interferes with normal body functions. Without intervention, these toxins may build up in the blood and result in coma and death of the affected animal. The clinical signs of amyloidosis are related to progressive kidney damage, and include excessive drinking and urination (polydipsia, polyuria), dehydration, poor coat quality, pale mucous membranes eg pale gums in the mouth, gingivitis (inflammation of the gums), lethargy, inappetance and weight loss.
2. Intensity of welfare impact
The clinical signs of amyloidosis vary in relation to the severity of kidney damage. Cats with significant amyloid deposition in the kidneys will generally feel unwell, as kidney damage starts to take place. They may be lethargic and weak, due to both the loss of protein and the build-up of toxic products in the blood. Affected cats have a diminished appetite but with excessive drinking and urination and episodes of vomiting. Some affected cats will have severe gingivitis (inflamed gums), which is painful, and this will result in further diminished appetite and subsequent weight loss. They may also experience abdominal pain as a result of the kidneys lack of ability to excrete certain waste products.
The condition is progressive and untreatable, leading to kidney failure as more healthy tissue is replaced with the amyloid substance. Cats can be given symptomatic treatment of chronic kidney failure. The rate of progression of liver failure is usually rapid in the late stages of the condition; once an affected cat has developed moderate build-up of waste products in the blood (azotemia and hyperphosphatemia).
3. Duration of welfare impact
Commonly cats develop amyloidosis between 1 and 5 years of age, although the progression of the disease in variable. For some affected cats, the deposition of amyloid may occur slowly, and kidney function may remain adequate for several years. For others, the deposition of amyloid may be rapid and severe, with kidney failure developing within one year.
4. Number of animals affected
Amyloidosis in cats is rarely reported in the scientific literature, and this may indicate the condition is rare or that it is underreported due to a lack of diagnosis of non-specific clinical signs and/or death before the disease is recognised or diagnosed. It has been most commonly described in Abyssinian cats.
5. Diagnosis
A veterinarian may be able to feel kidneys that are small, firm, and irregular on palpation, which may indicate amyloid deposition. However, a definitive diagnosis is made by identifying amyloid deposits in kidney biopsy samples. By the time clinical signs are noticeable, and amyloidosis is suspected, there will have been significant amyloid deposition and associated kidney damage, and therefore diagnosis is often made on post-mortem examination.
6. Genetics
Amyloidosis is a genetically inherited disease, which occurs within families in Abyssinian cats (ie a familial trait). Abyssinian cats have a genetically different version of serum amyloid A – which is more likely to form amyloid fibrils - compared to other breeds that have a low susceptibility for amyloidosis. However, the mode of inheritance in currently unknown, and further research is required to determine how these genes and amyloidosis susceptibility are inherited in cats.
7. How do you know if an animal is a carrier or likely to become affected?
A genetic test for identifying amyloidosis in cats is currently unavailable. We know that amyloidosis is more prevalent in Abyssinians cats than other breeds, and that the trait occurs within families, therefore the relatives and offspring of affected cats may be likely to carry the genetic mutations which predispose them to developing amyloidosis.
8. Methods and prospects for elimination of the problem
A genetic test for identifying amyloidosis in cats is currently unavailable. We know that amyloidosis is more prevalent in Abyssinians cats than other breeds, and that the trait occurs within families, therefore the relatives and offspring of affected cats may be likely to carry the genetic mutations which predispose them to developing amyloidosis.
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
Amyloidosis involves the extracellular deposition of insoluble, fibrous proteins – amyloids – into various tissues of the body. Proteins are formed when their building block molecules called amino acids are linked together. During this process, the protein commonly folds into characteristic 3D shapes; the shape being dependent upon the amino acids that link together to make it up and being essential for the protein’s normal function. Amyloids are inappropriately folded versions of normal proteins, which have aggregated together to form insoluble fibrils. A range of different proteins can form an amyloid, but the most common type is derived from serum amyloid A.
Serum amyloid A protein is formed mainly in the liver in response to inflammatory diseases and infections where it plays a role in cholesterol transport and as a chemoattractant in inflammatory processes (Urieli-Shoval et al 2000). Chronic inflammation or overstimulation of the pro-inflammatory cytokines results in a sustained abnormally high level of serum amyloid A. In such high concentrations, serum amyloid A splits into fragments that have an increased likelihood of clumping together Because of their rigid and misfolded structure these proteins function poorly and are difficult for the body to break down. They are removed from the cell to the extracellular space where they combine with other insoluble substances, to form amyloids. These amyloids are then deposited into various tissues of the body.
In Abyssinian cats, amyloids derived from serum amyloid A are primarily deposited in the kidney, and to a lesser extent, other tissues such as the spleen, stomach, intestines, thyroid, renal medulla and heart (DiBartola et al 1986b). (This is different to the case with Siamese and Oriental breeds, where amyloid deposits are primarily made in the liver (van der Linde-Sipman et al 1997)).
The main function of the kidneys is to regulate the chemical composition of the blood through the filtering of excessive fluid and waste products from it and the production of urine. Kidneys are made up of hundreds of thousands of small structures called nephrons, each of which comprises of a glomerulus and a tubule. Blood flowing through the kidney passes through the glomerulus - which is a network of fine capillaries - and in the process fluid and chemicals - including amino acids, the building blocks of proteins, are filtered out of the blood into the tubules. As this passes down the tubule much of this fluid is reabsorbed back into the blood, as are the amino acids, but any excess is collected in and eventually excreted in the urine.
In cats with amyloidosis, the fibrous amyloid substances build up and displace healthy tissue, disrupting the normal processes of the kidney. Affected kidneys become enlarged, inflamed and unable to function as normal. There is progressive damage as more kidney tissue is replaced with amyloid fibrils, and eventually this causes kidney failure, which can be fatal.
In affected cats, amyloid deposition is commonly found in the medullary interstitial and glomerular regions of the kidney, which are involved in the absorption of water and filtration of the blood. There is also thickening and scarring of tissue in the medullary interstitium of the kidney (fibrosis) and lesions and tissue death (necrosis) in the kidney papilla, which transports urine the calyces, cavities/spaces in the kidney where the urine is collected before passing onto the bladder (Chew et al 1982).
If amyloids are deposited in the glomeruli, where filtration of the blood occurs, proteins are lost from the blood and into the urine (proteinuria). Affected cats may have nonregenerative anaemia due to the continued loss of protein from the blood. They may also show abnormally high levels of nitrogen and phosphate in the blood (azotemia, hyperphosphatemia), and metabolic acidosis, which is excessive acidity of the blood, due to the kidneys’ reduced ability to excrete waste products, toxins and acid from the blood (Chew et al 1982). Without intervention, these toxins may build up in the blood and cause coma and death.
Abyssinian cats may have kidneys that are small, firm, and irregular on abdominal palpation by the veterinarian. The clinical signs of amyloidosis relate to progressive kidney damage caused by the condition and include excessive drinking and urination (polydipsia, polyuria) - as a result of the reduced ability to concentrate the urine - which can lead to dehydration. There may be poor coat quality, pallor or yellowing of mucous membranes (eg in the mouth) and gingivitis (inflammation of the gums). Cats may become lethargic, and lose an appetite for food, resulting in weight loss (Johnson et al 1996).
2. Intensity of welfare impact
The clinical signs of amyloidosis are a result of kidney failure and vary according to the severity of kidney damage. Small amyloid masses pose little clinical problem but larger depositions cause significant damage to the kidney. Cats with amyloid deposition in the kidneys will generally feel unwell, as impairment to kidney function starts to take place. They may be lethargic and weak, due to both the loss of protein and the build-up of toxic water product in the blood. Affected cats have a diminished appetite but with excessive drinking and urination and episodes of vomiting. Some affected cats will have severe gingivitis (inflamed gums), which is painful, and this will result in diminished appetite and subsequent weight loss. They may also experience abdominal pain as a result of the kidneys’ lack of ability to excrete waste products.
The condition is progressive, and leads to kidney failure as more healthy tissue is replaced with the amyloid substance. Cats can be given symptomatic treatment of chronic kidney failure but there is no specific treatment to prevent the development of amyloidosis or promote amyloid breakdown. The rate of progression of kidney failure is usually rapid in the late stages of the condition; once an affected cat has developed moderate build-up of waste products in the blood (azotemia and hyperphosphatemia). Underlying inflammatory disease is not commonly detected, but any concomitant infections should be treated appropriately.
3. Duration of welfare impact
The course of familial amyloidosis varies in severity and progression but commonly cats develop amyloidosis between 1 and 5 years of age (Paltrinieri et al 2015). For some affected cats, the deposition of amyloid may occur slowly, and kidney function may remain adequate for several years. For others, the deposition of amyloid may be rapid and severe, with kidney failure developing within one year (van der Linde-Sipman et al 1997).
4. Number of animals affected
Reports of amyloidosis in cats is rare in the scientific literature, and this may indicate the condition is rare or that it is underreported due to a lack of diagnosis of non-specific clinical signs and the early-onset fatality of the disease. It has been most commonly described in Abyssinian cats (Boyce et al 1984, DiBartola et al 1986a, Johnson et al 1989), although there are no specific data on the prevalence of the condition in cats.
5. Diagnosis
A veterinarian may be able to feel kidneys that are small, firm, and irregular on palpation, which may indicate chronic kidney failure. However, a definitive diagnosis is made by identifying amyloid deposits in kidney biopsy samples. Congo red dye is used to stain amyloids in tissue samples in order to accurately diagnose amyloidosis (Linke 2006). A high level of urinary excretion of serum amyloid A may be useful to detect familial amyloidosis before the onset of clinical signs (Paltrinieri et al 2015). However, by the time clinical signs are noticeable, and amyloidosis is suspected, there will have been significant amyloid deposition and associated damage, and therefore diagnosis is often made on post-mortem examination.
6. Genetics
Amyloidosis is a genetically inherited disease that occurs within families in Abyssinian cats (i.e. a familial trait). Analysis of the pedigrees of 62 Abyssinians cats with amyloidosis showed that certain ancestor cats were significantly more common in the pedigrees of affected cats than in those of unaffected cats in the randomly selected sample (DiBartola et al 1986a). The higher incidence of amyloidosis in Abyssinian cats than in other breeds may be linked to three differences in the amino acid sequence of the amyloid protein AA from an Abyssinian cat and a domestic short hair cat (which has low incidence of amyloidosis; Johnson et al 1989). There are a minimum of three genes and multiple alleles for serum amyloid A production in the Abyssinian cat (Harats et al 1991). However, the mode of inheritance is currently unknown, and further research is required to determine how these genes and amyloidosis susceptibility are inherited in cats.
7. How do you know if an animal is a carrier or likely to become affected?
A genetic test for identifying amyloidosis in cats is currently unavailable. We know that amyloidosis is more prevalent in Abyssinians cats than in other breeds, and that the trait occurs within families, therefore the relatives and offspring of affected cats may be likely to carry the genetic mutations which predispose them to developing amyloidosis.
8. Methods and prospects for elimination of the problem
Although the genes involved in amyloidosis in Abyssinian cats have been identified, the mode of inheritance is not known, and therefore advice for elimination of the disease is limited (Meyers-Wallen 2003). In addition to the occurrence of amyloidosis-associated genes, other factors such as infections and inflammatory processes are involved in the development of amyloidosis (Rossum et al 2004). Further genetic testing is required including the development of screening tools to identify cats that are likely to become affected. In the absence of further information, it is recommended that breeding from affected cats is avoided, and from those with severely affected relatives, including grandparents, siblings, previous offspring and siblings of parents (Farrell et al 2015).
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
Boyce JT, DiBartola SP, Chew DJ and Gasper PW (1984) Familial renal amyloidosis in Abyssinian cats. Veterinary Pathology 21: 33–8
Chew DJ, DiBartola SP, Boyce JT and Gasper PW (1982) Renal amyloidosis in related Abyssinian cats.. Journal of the American Veterinary Medical Association 181: 139–42
DiBartola SP, Hill RL, Fechheimer NS and Powers JD (1986a) Pedigree analysis of Abyssinian cats with familial amyloidosis. American Journal Of Veterinary Research 47: 2666–8
DiBartola SP, Tarr MJ and Benson MD (1986b) Tissue distribution of amyloid deposits in Abyssinian cats with familial amyloidosis. Journal of Comparative Pathology 96: 387–398
Farrell LL, Schoenebeck JJ, Wiener P, Clements DN and Summers KM (2015) The challenges of pedigree dog health: approaches to combating inherited disease. Canine Genetics and Epidemiology 2: 3
Harats N, DiBartola SP, Benson D and Kluve-Beckerman B (1991) Amyloid and Amyloidosis 1990. In Natvig JB, Førre Ø, Husby G, Husebekk A, Skogen B, Sletten K, and Westermark P (eds.) VIth International Symposium on Amyloidosis August 5–8, 1990 pp. 32–35. Springer Netherlands, Oslo, Norway
Johnson KH, Sletten K, Werdin RE, Westermark GT, O’Brien TD and Westermark P (1989) Amino acid sequence variations in protein AA of cats with high and low incidences of AA amyloidosis. Comparative Biochemistry And Physiology. B, Comparative Biochemistry 94: 765–8
Johnson KH, Westermark P, Sletten K and O’Brien TD (1996) Amyloid proteins and amyloidosis in domestic animals. Amyloid 3: 270-289
van der Linde-Sipman JS, Niewold TA, Tooten PCJ, de Neijs-Backer M and Gruys E (1997) Generalized AA-amyloidosis in Siamese and Oriental cats. Veterinary Immunology and Immunopathology 56: 1–10
Linke RP (2006) Congo Red Staining of Amyloid: Improvements and Practical Guide for a More Precise Diagnosis of Amyloid and the Different Amyloidoses. In Uversky VN and Fink AL (eds.) Protein Misfolding, Aggregation, and Conformational Diseases pp. 239–276Volume 4 o.. Springer US, Boston, MA
Meyers-Wallen VN (2003) Ethics and genetic selection in purebred dogs. Reproduction In Domestic Animals 38: 73–6
Paltrinieri S, Sironi G, Giori L, Faverzani S and Longeri M (2015) Changes in Serum and Urine SAA Concentrations and Qualitative and Quantitative Proteinuria in Abyssinian Cats with Familial Amyloidosis: A Five-year Longitudinal Study (2009-2014). Journal of Veterinary Internal Medicine 29: 505–512
Rossum M van, Asten FJ van, Rofina J, Lenstra JA, Benson MD and Gruys E (2004) Analysis of cDNA sequences of feline SAAs. Amyloid 11: 38-43
Urieli-Shoval S, Linke RP and Matzner Y (2000) Expression and function of serum amyloid A, a major acute-phase protein, in normal and disease states.. Current opinion in hematology 7: 64–9
© UFAW 2016
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