Keshan disease is a rare but serious form of cardiomyopathy, a condition that affects the heart muscle, and is primarily caused by a combination of severe dietary selenium deficiency and a viral trigger. The disease was first discovered in Keshan County, China, in 1935 and has historically been endemic in a broad belt stretching across the country. While rare in most developed countries due to varied dietary intake, it remains a public health concern in specific, remote, and impoverished areas with selenium-poor soil.
The Critical Role of Selenium Deficiency
Selenium is an essential trace mineral that plays a vital role in human health through its incorporation into selenoproteins. These proteins are critical for numerous bodily functions, particularly the body’s antioxidant defense system. One crucial selenoprotein is glutathione peroxidase (GPx), which helps protect cells from oxidative damage caused by reactive oxygen species.
In regions with selenium-poor soil, locally grown food contains very little of this mineral, leading to inadequate dietary intake and selenium deficiency. In a selenium-deficient state, the heart muscle becomes highly susceptible to oxidative stress and damage, laying the groundwork for developing cardiomyopathy. Research has consistently shown a strong correlation between low selenium status in residents of endemic areas and the occurrence of Keshan disease. Large-scale supplementation programs using sodium selenite have effectively reduced disease incidence, providing strong evidence for selenium's critical role.
The Viral Trigger: Coxsackievirus
While selenium deficiency is a prerequisite for the disease, it is not the sole cause; not all individuals with low selenium develop Keshan disease. The condition is thought to be triggered by an environmental factor, most notably a coxsackievirus B infection. Research involving selenium-deficient mice infected with coxsackievirus B demonstrated a significant increase in the virus's virulence, turning an otherwise benign virus into a highly aggressive pathogen that targets the heart. This suggests a two-pronged mechanism:
- Predisposition: Chronic selenium deficiency weakens the heart's antioxidant defenses, leaving it vulnerable to damage.
- Trigger: A coxsackievirus infection exploits this vulnerability, causing severe myocardial injury and leading to the clinical manifestations of Keshan disease.
Genetic Predisposition and Other Factors
Beyond nutrition and viral infection, genetic factors also play a role in Keshan disease. Research has identified specific genetic mutations and polymorphisms that contribute to susceptibility. For example, mutations in the GPx-1 gene, which codes for the selenium-dependent enzyme, have been linked to an increased incidence of the disease. Furthermore, studies have shown that having a family history of the disease increases risk, suggesting an inherited component. Additional factors, such as deficiencies in other nutrients like vitamin E, have also been proposed as contributing elements.
Different Clinical Forms of Keshan Disease
Keshan disease manifests in four different clinical forms, each with distinct symptoms and progression:
- Acute: A rapid onset, often affecting children, characterized by severe heart failure, cardiogenic shock, and pulmonary edema. Symptoms include dizziness, nausea, and shortness of breath.
- Subacute: A slower onset than the acute form, featuring signs of both congestive heart failure and cardiogenic shock. Most common in children aged 2-5 years.
- Chronic: Characterized by an insidious onset and slowly progressing heart failure due to dilated heart chambers, thinning heart walls, and extensive myocardial fibrosis.
- Latent: The most common form today, with few or no apparent symptoms, compensated heart function, and only minor ECG abnormalities.
Comparison: Keshan Disease vs. Idiopathic Dilated Cardiomyopathy
| Feature | Keshan Disease (KD) | Idiopathic Dilated Cardiomyopathy (IDCM) |
|---|---|---|
| Primary Cause | Selenium deficiency + viral trigger | Unknown (idiopathic) |
| Geographical Link | Endemic to selenium-deficient regions | No specific geographical link |
| Age Group | Affects children and women of child-bearing age | Can affect any age, more common in adults |
| Prevalence | Historically high in certain areas of China, now lower due to public health interventions | Varied prevalence globally, not linked to specific soil conditions |
| Etiology | Multifactorial: nutritional, viral, genetic | Generally unknown; may involve genetic mutations, autoimmune issues, or prior viral myocarditis |
| Key Intervention | Selenium supplementation is a highly effective prevention and treatment | Standard heart failure treatment; no specific supplement for causation |
Conclusion
Understanding what Keshan disease is caused by reveals a complex interplay of environmental, viral, and genetic factors. The primary etiological link is a severe deficiency of the trace mineral selenium, which is exacerbated by a specific viral infection. Public health efforts focused on selenium supplementation have dramatically reduced the incidence of this endemic cardiomyopathy in at-risk regions. While the acute and subacute forms are now less common, chronic and latent cases still exist and highlight the importance of continued monitoring and intervention. Effective prevention depends on addressing the underlying nutritional deficiencies, particularly in socioeconomically disadvantaged communities where the risk remains highest.
For more information on the history and epidemiology of Keshan disease, see this review article from the Asia Pacific Journal of Clinical Nutrition(https://apjcn.qdu.edu.cn/21_3_1.pdf).
