What is Keshan disease?

Keshan Disease: An Endemic Cardiomyopathy Related to Selenium Deficiency

Keshan disease is an endemic cardiomyopathy caused primarily by selenium deficiency that occurs in regions with selenium-deficient soil, particularly in remote mountainous areas of China.

Definition and Etiology

Keshan disease is named after Keshan County in northeastern China, where it was first reported in 1935 1. It is a specific type of dilated cardiomyopathy with the following key characteristics:

• Primary cause: Severe selenium deficiency in the local food chain due to selenium-deficient soil 2, 3
• Contributing factors:
  • Viral infections (particularly Coxsackie virus) may act as co-factors 4
  • T-2 toxin (a mycotoxin) exposure may exacerbate cardiac damage in selenium-deficient individuals 5
  • Genetic susceptibility (variations in glutathione peroxidase-1 gene) 6

Pathophysiology

The disease develops through several mechanisms:

• Antioxidant system impairment: Selenium is essential for glutathione peroxidase (GPx) activity, a key antioxidant enzyme that protects cardiac tissue from oxidative damage 2, 6
• Increased susceptibility to viral damage: Selenium deficiency may allow viruses like Coxsackie B to cause more severe myocardial damage 4
• Endoplasmic reticulum stress: Selenium deficiency aggravates T-2 toxin-induced cardiomyocyte injury through increased ER stress 5

Clinical Manifestations

Keshan disease primarily presents with:

• Congestive heart failure
• Acute heart failure episodes
• Cardiac arrhythmias
• Cardiomegaly (increased cardiothoracic ratio)
• Abnormal ECG findings including evidence of increased cardiac load 1, 6

Epidemiology

The disease shows specific demographic and geographic patterns:

• High-risk populations: Children under 15 years of age and women of childbearing age 3
• Geographic distribution: Endemic in regions with selenium-deficient soil, particularly remote and mountainous areas of China 1
• Socioeconomic factors: More prevalent in socioeconomically disadvantaged areas with poor housing, income, education, and limited healthcare access 1

Diagnosis

Diagnosis is based on:

• Clinical cardiac symptoms
• Residence in an endemic area
• Family history of Keshan disease
• Low blood selenium levels (<0.12 ppm in hair samples)
• Reduced glutathione peroxidase-1 (GPx-1) activity 3, 6
• Increased cardiothoracic ratio and Tei index (myocardial performance index) 6
• Abnormal ECG findings

Prevention and Treatment

The most effective approach is prevention:

• Selenium supplementation: Weekly administration of 0.5-1 mg sodium selenite has been shown to dramatically reduce incidence rates from 9.5-13.5/1000 to 1-2/1000 in high-risk children 3
• Public health measures: Improving selenium content in local food chains through soil enrichment or dietary diversification
• Risk factor identification: Monitoring GPx-1 activity in high-risk populations 6

Clinical Significance

Keshan disease demonstrates the critical importance of trace elements in cardiovascular health. The dramatic reduction in disease incidence following selenium supplementation programs highlights the effectiveness of targeted nutritional interventions in preventing serious endemic diseases 3, 1.

Pitfalls and Caveats

• Multifactorial etiology: While selenium deficiency is necessary, it may not be sufficient alone to cause Keshan disease; viral infections and other factors likely contribute 4
• Differential diagnosis: Other forms of dilated cardiomyopathy must be ruled out
• Prevention focus: Treatment of established disease is less effective than prevention through selenium supplementation
• Monitoring challenges: In remote areas, access to selenium testing and cardiac monitoring may be limited

Keshan disease remains a significant public health challenge in certain regions, requiring continued attention to selenium status monitoring and supplementation programs in vulnerable populations.