Samoyed hereditary glomerulopathy

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Healthy Samoyed dog Shuskey.jpg
Healthy Samoyed dog

Samoyed hereditary glomerulopathy (SHG) is a hereditary, X-linked, noninflammatory disease of the renal glomeruli, occurring in the Samoyed breed of dog. The disease has been shown to be a model for Alport syndrome in humans [1] in that the disease resembles that of the human disease. Because of this, it is sometimes referred to by the name given to the disease in humans when referring to the conditions in Samoyed dogs. Alternatively, it may also be known as X-linked hereditary nephritis. Genetically, the trait is inherited as a sex-linked, genetically dominant disease, [2] and thus affects male dogs to a greater degree than female dogs, since males only have one X chromosome.

Contents

Description

SHG is caused by a nonsense mutation in codon 1027 of the COL4A5 gene on the X chromosome (glycine to stop codon), which is similar to Alport syndrome in humans. [3] The disease is simply inherited, X-linked dominant, with males generally having more severe symptoms than females. Clinically, from the age of three to four months, proteinuria in both sexes is seen. In dogs older than this, kidney failure in combination with more or less pronounced hearing loss occurs swiftly, and death at the age of 8 to 15 months is expected. In heterozygous females, whereby only one of the two X chromosomes carry the mutation, the disease develops slowly. [4] [5]

The disease is specific to the Samoyed in that, the Samoyed, is the only breed of dog to show the more rapid progression to kidney failure and death, as well as affecting males to a much more severe degree than females. The Samoyed, however is not the only breed of dog to suffer from life-threatening renal diseases. Proteinuria has been found consistently in Samoyeds, Doberman Pinschers, and Cocker spaniels. [6] [7]

Diagnosis

Affected male and carrier female dogs generally begin to show signs of the disease at two to three months of age, with proteinuria. By three to four months of age, symptoms include for affected male dogs: bodily wasting and loss of weight, proteinuria & hypoalbuminemia. Past nine months of age, hypercholesterolemia may be seen. [1] In the final stages of the disease, at around 15 months of age for affected males, symptoms are reported as being kidney failure, hearing loss and death. Since the condition is genetically dominant, diagnosis would also include analysis of the health of the sire and dam of the suspected affected progeny if available.

Treatment

The disease can be treated only to slow down the development, by use of cyclosporine A [5] and ACE inhibitors, but not stopped or cured. [8]

Related Research Articles

<span class="mw-page-title-main">Proteinuria</span> Presence of an excess of serum proteins in the urine

Proteinuria is the presence of excess proteins in the urine. In healthy persons, urine contains very little protein, less than 150 mg/day; an excess is suggestive of illness. Excess protein in the urine often causes the urine to become foamy. Severe proteinuria can cause nephrotic syndrome in which there is worsening swelling of the body.

<span class="mw-page-title-main">Samoyed dog</span> Dog breed

The Samoyed is a breed of medium-sized herding dogs with thick, white, double-layer coats. They are spitz-type dogs which take their name from the Samoyedic peoples of Siberia. Descending from the Nenets Herding Laika, they are domesticated animals that assist in herding, hunting, protection and sled-pulling.

<span class="mw-page-title-main">IgA nephropathy</span> Disease of the kidney

IgA nephropathy (IgAN), also known as Berger's disease, or synpharyngitic glomerulonephritis, is a disease of the kidney and the immune system; specifically it is a form of glomerulonephritis or an inflammation of the glomeruli of the kidney. Aggressive Berger's disease can attack other major organs, such as the liver, skin and heart.

<span class="mw-page-title-main">Alport syndrome</span> Medical condition

Alport syndrome is a genetic disorder affecting around 1 in 5,000-10,000 children, characterized by glomerulonephritis, end-stage kidney disease, and hearing loss. Alport syndrome can also affect the eyes, though the changes do not usually affect vision, except when changes to the lens occur in later life. Blood in urine is universal. Proteinuria is a feature as kidney disease progresses.

<span class="mw-page-title-main">Glomerulonephritis</span> Term for several kidney diseases

Glomerulonephritis (GN) is a term used to refer to several kidney diseases. Many of the diseases are characterised by inflammation either of the glomeruli or of the small blood vessels in the kidneys, hence the name, but not all diseases necessarily have an inflammatory component.

<span class="mw-page-title-main">X-linked recessive inheritance</span> Mode of inheritance

X-linked recessive inheritance is a mode of inheritance in which a mutation in a gene on the X chromosome causes the phenotype to be always expressed in males and in females who are homozygous for the gene mutation, see zygosity. Females with one copy of the mutated gene are carriers.

<span class="mw-page-title-main">Focal segmental glomerulosclerosis</span> Kidney disease

Focal segmental glomerulosclerosis (FSGS) is a histopathologic finding of scarring (sclerosis) of glomeruli and damage to renal podocytes. This process damages the filtration function of the kidney, resulting in protein presence in the urine due to protein loss. FSGS is a leading cause of excess protein loss—nephrotic syndrome—in children and adults. Signs and symptoms include proteinuria and edema. Kidney failure is a common long-term complication of the disease. FSGS can be classified as primary, secondary, or genetic, depending on whether a particular toxic or pathologic stressor or genetic predisposition can be identified as the cause. Diagnosis is established by renal biopsy, and treatment consists of glucocorticoids and other immune-modulatory drugs. Response to therapy is variable, with a significant portion of patients progressing to end-stage kidney failure. An American epidemiological study 20 years ago demonstrated that FSGS is estimated to occur in 7 persons per million, with males and African-Americans at higher risk.

Thin basement membrane disease is, along with IgA nephropathy, the most common cause of hematuria without other symptoms. The only abnormal finding in this disease is a thinning of the basement membrane of the glomeruli in the kidneys. Its importance lies in the fact that it has a benign prognosis, with patients maintaining a normal kidney function throughout their lives.

Familial renal disease is an uncommon cause of kidney failure in dogs and cats. Most causes are breed-related (familial) and some are inherited. Some are congenital. Renal dysplasia is a type of familial kidney disease characterized by abnormal cellular differentiation of kidney tissue. Dogs and cats with kidney disease caused by these diseases have the typical symptoms of kidney failure, including weight loss, loss of appetite, depression, and increased water consumption and urination. A list of familial kidney diseases by dog and cat breeds is found below.

<span class="mw-page-title-main">Nail–patella syndrome</span> Medical condition

Nail–patella syndrome is a genetic disorder that results in small, poorly developed nails and kneecaps, but can also affect many other areas of the body, such as the elbows, chest, and hips. The name "nail–patella" can be very misleading because the syndrome often affects many other areas of the body, including even the production of certain proteins. The severity of these effects varies depending on the individual. It is also referred to as iliac horn syndrome, hereditary onychoosteodysplasia, Fong disease or Turner–Kieser syndrome.

<span class="mw-page-title-main">Glomerular basement membrane</span>

The glomerular basement membrane of the kidney is the basal lamina layer of the glomerulus. The glomerular endothelial cells, the glomerular basement membrane, and the filtration slits between the podocytes perform the filtration function of the glomerulus, separating the blood in the capillaries from the filtrate that forms in Bowman's capsule. The glomerular basement membrane is a fusion of the endothelial cell and podocyte basal laminas, and is the main site of restriction of water flow. Glomerular basement membrane is secreted and maintained by podocyte cells.

<span class="mw-page-title-main">Dent's disease</span> Medical condition

Dent's disease is a rare X-linked recessive inherited condition that affects the proximal renal tubules of the kidney. It is one cause of Fanconi syndrome, and is characterized by tubular proteinuria, excess calcium in the urine, formation of calcium kidney stones, nephrocalcinosis, and chronic kidney failure.

<span class="mw-page-title-main">Collagen, type IV, alpha 5</span> Protein-coding gene in humans

Collagen alpha-5(IV) chain is a protein that in humans is encoded by the COL4A5 gene.

<span class="mw-page-title-main">Collagen, type IV, alpha 1</span> Protein found in humans

Collagen alpha-1(IV) chain (COL4A1) is a protein that in humans is encoded by the COL4A1 gene on chromosome 13. It is ubiquitously expressed in many tissues and cell types. COL4A1 is a subunit of the type IV collagen and plays a role in angiogenesis. Mutations in the gene have been linked to diseases of the brain, muscle, kidney, eye, and cardiovascular system. The COL4A1 gene also contains one of 27 SNPs associated with increased risk of coronary artery disease.

<span class="mw-page-title-main">Collagen, type IV, alpha 4</span> Protein found in humans

Collagen alpha-4(IV) chain is a protein that in humans is encoded by the COL4A4 gene.

Glomerulonephrosis is a non-inflammatory disease of the kidney (nephrosis) presenting primarily in the glomerulus as nephrotic syndrome. The nephron is the functional unit of the kidney and it contains the glomerulus, which acts as a filter for blood to retain proteins and blood lipids. Damage to these filtration units results in important blood contents being released as waste in urine. This disease can be characterized by symptoms such as fatigue, swelling, and foamy urine, and can lead to chronic kidney disease and ultimately end-stage renal disease, as well as cardiovascular diseases. Glomerulonephrosis can present as either primary glomerulonephrosis or secondary glomerulonephrosis.

Lachiewicz–Sibley syndrome is a rare autosomal dominant disorder characterized by preauricular pits and renal disease. Persons with this disease may have hypoplasic kidneys or proteinuria. This disease was first described in a Caucasian family of British and Irish descent that emigrated to Ohio in the 19th century before settling in Nebraska. Many of the members of this family still live in Nebraska, although the relatives are now scattered throughout the country.

Fanconi syndrome or Fanconi's syndrome is a syndrome of inadequate reabsorption in the proximal renal tubules of the kidney. The syndrome can be caused by various underlying congenital or acquired diseases, by toxicity, or by adverse drug reactions. It results in various small molecules of metabolism being passed into the urine instead of being reabsorbed from the tubular fluid. Fanconi syndrome affects the proximal tubules, namely, the proximal convoluted tubule (PCT), which is the first part of the tubule to process fluid after it is filtered through the glomerulus, and the proximal straight tubule, which leads to the descending limb of loop of Henle.

<span class="mw-page-title-main">Epstein syndrome</span> Medical condition

Epstein syndrome is a rare genetic disease characterized by a mutation in the MYH9 gene in nonmuscle myosin. This disease affects the patient's renal system and can result in kidney failure. Epstein Syndrome was first discovered in 1972 when two families had similar symptoms to Alport syndrome. Epstein syndrome and other Alport-like disorders were seen to be caused by mutations in the MYH9 gene, however, Epstein syndrome differs as it was more specifically linked to a mutation on the R702 codon on the MYH9 gene. Diseases with mutations on the MYH9 gene also include May–Hegglin anomaly, Sebastian syndrome and Fechtner syndrome.

References

  1. 1 2 Jansen, B; Valli, VE; Thorner, P; Baumal, R; Lumsden, JH (1987). "Samoyed hereditary glomerulopathy: serial, clinical and laboratory (urine, serum biochemistry and hematology) studies". Canadian Journal of Veterinary Research. 51 (3): 387–93. PMC   1255344 . PMID   3651895.
  2. Jansen, B; Tryphonas L; Wong J; Thorner P; Maxie MG; Valli VE; Baumal R; Basrur PK. (June 1986). "Mode of inheritance of Samoyed hereditary glomerulopathy: an animal model for hereditary nephritis in humans". J Lab Clin Med. (6). 107 (6): 551–5. PMID   3711721.
  3. Jansen, B; Tryphonas, L; Wong, J; Thorner, P; Maxie, MG; Valli, VE; Baumal, R; Basrur, PK (1986). "Mode of inheritance of Samoyed hereditary glomerulopathy: an animal model for hereditary nephritis in humans". The Journal of Laboratory and Clinical Medicine. 107 (6): 551–5. PMID   3711721.
  4. Zheng, K; Thorner, PS; Marrano, P; Baumal, R; McInnes, RR (1994). "Canine X chromosome-linked hereditary nephritis: a genetic model for human X-linked hereditary nephritis resulting from a single base mutation in the gene encoding the alpha 5 chain of collagen type IV". Proceedings of the National Academy of Sciences of the United States of America. 91 (9): 3989–93. Bibcode:1994PNAS...91.3989Z. doi: 10.1073/pnas.91.9.3989 . PMC   43708 . PMID   8171024.
  5. 1 2 Chen, D.; Jefferson, B; Harvey, SJ; Zheng, K; Gartley, CJ; Jacobs, RM; Thorner, PS (2003). "Cyclosporine A Slows the Progressive Renal Disease of Alport Syndrome (X-Linked Hereditary Nephritis): Results from a Canine Model". Journal of the American Society of Nephrology. 14 (3): 690–8. doi: 10.1097/01.ASN.0000046964.15831.16 . PMID   12595505.
  6. Wilcock, BP; Patterson, JM (1979). "Familial glomerulonephritis in Doberman pinscher dogs". The Canadian Veterinary Journal. 20 (9): 244–9. PMC   1789598 . PMID   498006.
  7. Steward, A. P.; MacDougall, D. F. (1984). "Familial nephropathy in the Cocker Spaniel". Journal of Small Animal Practice. 25: 15–24. doi:10.1111/j.1748-5827.1984.tb00475.x.
  8. Grodecki, K; Gains, M; Baumal, R; Osmond, D; Cotter, B; Valli, V; Jacobs, R (1997). "Treatment of X-linked hereditary nephritis in samoyed dogs with angiotensin converting enzyme (ACE) inhibitor". Journal of Comparative Pathology. 117 (3): 209–25. doi:10.1016/S0021-9975(97)80016-3. PMID   9447482.

Further reading