Introductory to Chediak-Higashi Syndrome
Chediak-Higashi Syndrome (CHS) is a rare genetic disorder primarily found in blue-smoke Persian cats, which exhibit a diluted smoke blue coat color and yellow-green irises. This syndrome is characterised by a comprehensive combination of immunodeficiency, neurological abnormalities, and distinctive physical features.
Importance of Studying CHS
The importance of Persian cats as one of the breeds most commonly affected by CHS makes them a crucial model for studying this syndrome and enhancing the understanding of genetic mutations and genetic diagnosis.
Complexities in Studying CHS
| Potentials | Limitations |
|---|---|
| ✧ Ability to identify specific genetic mutations | ✧ Potentially overlooking variations in genetics |
| ✧ Adoption of better diagnostic tools and management strategies | ✧ Inability to perform large-scale studies, hence increasing the difficulty in drawing statistically significant conclusions |
| ✧ Advancement in comparative medicine | ✧ Ethical issues |
| ✧ Raising awareness about CHS |
Clinical Signs and Analysis of Chediak-Higashi Syndrome in Cats
Overview of Clinical Signs
- Bleeding for an abnormally long period
- Cat’s eyes will reflect a red eyeshine when exposed to light
- Excessive blinking and eye-watering
- Development of cataracts at an early age (often before 3 months)
- Increased susceptibility to infections
- Light-colored or diluted fur and skin
- Swelling of lymph nodes
- May exhibit photophobia
- Developmental delays in kittens
Fig.1 Comparison of typical normal blue smoke and Chediak-Higashi Syndrome blue smoke in Persian cats
Analysis of Clinical Signs of CHS
1. Lysosomal Dysfunction
(A collection of rare diseases with various causes linked by the malfunctioning of the lysosomes, function of breaking down waste)
Chediak-Higashi Syndrome is marked by an accumulation of vesicles or granules in the cell’s cytoplasm. In diagnosed cats, a defect impairs the normal functioning of lysosomes, which is a membrane-bound fluid-filled sacs that serve as the cell’s disposal system. Lysosomes typically fuse with unwanted or aged organelles and large molecules within the cytoplasm, thereby breaking them down into their basic components.
2. Partial Albinism
(A rare and lethal immune disorder marked by pigmentary dilution and varying degrees of cellular immunodeficiency, color of fur and skin)
In cats diagnosed with Chediak-Higashi Syndrome, the genetic defect significantly prevents lysosomes from effectively bonding with other cell vesicles during normal fusion and fission processes. Thus, this contributes to an accumulation of lysosomes around the cell nucleus, consequently disrupting normal cellular function.
3. Immunological Implications
(Enlarged melanin granules, lighter color coat, reddish eyes & photophobia)
Subsequently, this syndrome causes partial albinism in both the fur and eyes of cats due to an accumulation of enlarged melanin granules in cells, resulting in a lighter or whitish coat. Reddish-orange light reflecting from the retina of affected cats often surfaces as a result. Cats with this syndrome are generally sensitive to light and may even develop photophobia, which is an aversion to bright environments.
4. Coagulation Issues
(Enlarged granules in blood & kidney cells, prolong blood clotting & bacterial infections)
Similarly, afflicted cats experience compromised immune function, with enlarged granules present in their white and red blood cells as well as in kidney cells. This thus plays a role to an increased vulnerability to bacterial infections. Conversely, abnormally prolonged blood clotting times in these cats emerge, giving rise to excessive bleeding after surgical procedures or injuries.
Fig.2 Physical appearance of a Persian cat diagnosed with Chediak-Higashi Syndrome
Fig 3. Blood smear displaying distinctive large cytoplasmic granules in neutrophils and eosinophils (A), neutrophils (B), and lymphocytes (C, D).
Genetic and Molecular Mechanisms
Chediak-Higashi syndrome is observed in Persian cats selectively bred for their distinctive yellow eye color and “blue smoke” coat color. The underlying genetics of this syndrome entails a mutation in the CHS1/LYST gene, which encodes the creation of a protein essential for lysosome transport.
Repercussions of this Mutation
- Disrupts normal cellular processes.
- Increases the risk of inflammatory disorders.
- Develops vision abnormalities.
- Contributes to the accumulation of large cytoplasmic granules in blood cells (e.g., neutrophils and eosinophils).
Inheritance Pattern
The inheritance pattern associated with CHS is autosomal recessive, showcasing the complete penetrance of the syndrome.
- Cats that possess two defective gene copies, with each gene inherited from each parent cat, will manifest the clinical symptoms of the syndrome.
- Conversely, those who inherit only one defective copy will remain asymptomatic. However, they will be carriers capable of passing this gene to approximately half of their offspring.
Although the genes responsible for CHS are connected, the specific coat and eye colors remain unclear due to the broad variation in phenotypic expressions and the intricacy of genetics.
Fig. 4 CHS in Persian cats in this experiment are at 5.5 months of age. Diagnosed with CHS cat (left) has a lighter coat color than the non-affected cat (right)
Fig. 5 Pedigree of resurrected feline model of Chediak-Higashi syndrome via assisted reproduction.
- Half-filled symbols represent predicted carrier status based on the presence of the mutant allele from genotyping.
- Male Smokey (arrow) is heterozygous, which did not exhibit any CHS-related symptoms throughout his life.
- 12OTHN2 and 12ODH5 do not carry any CHS alleles.
- The genotype of 19529 remains unknown as he did not produce any amplicons.
How is it Diagnosed and Treated?
Currently, there are no genetic tests available to identify Chediak-Higashi Syndrome. However, affected cats can be diagnosed through a blood smear test. This test involves:
- Analyzing a blood sample under a microscope.
- Identification of large cytoplasmic granules in neutrophils and eosinophils.
- Evaluation of the morphology of white blood cells.
Fig.6 A typical blood smear test
Diagnosis
- Initial Steps
To begin with, your veterinarian will start off by gathering a full medical history and conducting a detailed examination. - Blood Tests
- In your cat’s blood tests, the veterinarian might notice a decrease in the number of white blood cells.
- If the blood is examined under a microscope, the veterinarian might observe abnormalities in the white blood cells due to the presence of large granules.
- In some cases, a tissue biopsy may be required to inspect melanocytes in skin pigment cells to diagnose CHS.
- Physical Examination
- A thorough physical exam is conducted to gather a background health history of your cat leading up to the onset of symptoms.
- A complete blood profile will be performed, including:
- A chemical blood profile
- A complete blood count
- A urinalysis
- Genetic Profiling
If your cat fits the genetic profile, the veterinarian will then proceed to execute the blood smear test for CHS using the blood sample collected. - Test Results
These tests will reveal large granules in cells and a lower number of immune cells in the blood.
Treatment
- Most cats diagnosed with Chediak-Higashi syndrome do not need treatment. However, they should still receive regular veterinary checkups to monitor their health.
- The veterinarian would likely take special precautions when carrying out blood draws or any necessary procedures on your cat to prevent further bleeding.
- A pre-surgical platelet transfusion may be suggested to prevent excessive bleeding if your cat is undergoing surgery.
- Additionally, the veterinarian will provide your cat with vitamin C to enhance blood cell and platelet function and reduce bleeding time.
- Be sure to keep these cats indoors to protect their delicate eyes and skin from the harmful effects of the sun due to their abnormal pigmentation.
- It is important to note that affected cats should never be bred, and their parents should be removed from breeding programs.
Conclusion
Ultimately, Chediak-Higashi syndrome is an extraordinary genetic disorder that significantly impacts Persian cats. This is signified by the multitude of clinical signs, including immune dysfunction and bleeding disorders. By acknowledging the sophisticated mechanism of genetics and molecules behind CHS, particularly the role of the CHS1/LYST gene, we can then apprehend the causation of this medical condition.
On top of that, further research is essential for the genetic basis of CHS, which could potentially contribute to the development of genetic tests, supported by the advancement of modern technology, that could effectively and precisely identify the carriers and affected individuals.
References
- Genetic Welfare Problems of Companion Animals — Universities Federation for Animal Welfare
[Link](https://www.ufaw.org.uk/cats/persian—chediak-higashi-syndrome#:~:text=Cats%20with%20Che diak%2DHigashi%20syndrome%20are%20sensitive%20to%20light%2C%20and,the%20cells%2 0of%20the%20kidney) - Chediak-Higashi Syndrome in Cats – By Malcolm Weir, DVM, MSc, MPH; Catherine Barnette, DVM
Link - The Chediak-Higashi Syndrome of Cats – By J W Kramer, W C Davis, D J Prieur
Link - Chediak-Higashi Syndrome in Felis catus (domestic cat)
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