Leigh syndrome is a rare mitochondrial disorder characterized by acute necrosis of the basal ganglia and brainstem structures. This pathology manifests itself in severe neurological disorders, including regression of psychomotor development, seizures, muscle hypotonia and respiratory disorders. The disease has a progressive course and often leads to death in early childhood. The pathophysiological basis of the disease is a violation of oxidative phosphorylation in the mitochondria, which leads to energy deficiency of neurons.
History of the disease and interesting historical facts
The first description of the syndrome was made in 1951 by the English neurologist Archibald Ley, after whom the syndrome was named. In his work "Subacute necrotizing encephalomyelopathy in an infant" he described a clinical case of a two-year-old child with progressive neurological symptoms. It is interesting to note that the first studies showed a connection between the disease and a deficiency of vitamin B1 (thiamine), which was later refuted by more in-depth molecular genetic studies. "The discovery of the mitochondrial nature of the disease was a real breakthrough in understanding its pathogenesis," notes Professor Jones in his 1976 study.
Epidemiology
The incidence of Leigh syndrome is approximately 1 in 40,000 live births. According to a large international study conducted in 2018, the disease is diagnosed more often in boys (ratio 1.3:1). Mortality from this pathology is extremely high - about 70% patients die during the first year of life. It is noteworthy that the disease can manifest at any age, but most often the onset occurs between 3 months and 2 years of life.
Genetic predisposition to this disease
More than 75 different mutations are associated with the development of Leigh syndrome. The most common mutations are in the following genes:
- MT-ATP6 (mitochondrial DNA)
- NDUFV1 (nuclear DNA)
- NDUFS1 (nuclear DNA)
- PDHA1 (X-linked inheritance)
It is important to note that mutations in mitochondrial DNA are transmitted through the maternal line, which explains the inheritance patterns of the disease.
Risk factors for the development of this disease
The main risk factors are:
- Congenital metabolic disorders
- Toxic effects of cyanides and other respiratory chain inhibitors
- Carnitine and Coenzyme Q10 Deficiency
- Viral infections, especially herpes virus infection
A special role is played by such exogenous factors as hypoxia, hyperthermia and intoxication, which can provoke the development of symptoms in genetically predisposed individuals.
Diagnosis of this disease
The main symptoms include:
- Progressive muscle weakness
- Vomiting and difficulty swallowing
- Nystagmus and other oculomotor disorders
Laboratory studies reveal elevated levels of lactate in the blood and cerebrospinal fluid. MRI shows characteristic changes in the basal ganglia. Differential diagnosis requires excluding multiple sclerosis, encephalitis, and other metabolic disorders.
Treatment
General treatment is aimed at maintaining vital functions. Pharmacological therapy includes antioxidants and drugs that improve energy metabolism. Surgery may be required to correct complications. Additional treatments include diet therapy and rehabilitation measures.
List of drugs used to treat this disease
- Coenzyme Q10
- Thiamine
- Levocarnitine
- Vitamin E
- Antioxidant complexes
Disease monitoring
Control stages include regular determination of lactate levels, assessment of neurological status every 3 months. The prognosis remains serious despite the therapy. The main complications are multiple organ failure and irreversible neurological disorders.
Age-related features of the disease
In newborns, the disease often manifests itself as pseudostratification, in older children - as coordination disorders. In adults, the form is more benign, but with a predominance of mental disorders.
Questions and Answers
- What are the first signs of the disease? Initial symptoms usually include lethargy, refusal to eat, and vomiting.
- Can Leigh syndrome be cured? Unfortunately, a complete cure is impossible, but progression can be slowed down.
- How is the disease transmitted? The disease can be transmitted both in an autosomal recessive manner and through the maternal line.
Advice from Dr. Oleg Korzhikov
Parents often ask how to recognize the initial signs of the disease. It is important to pay attention to any changes in the child's behavior, especially if they are accompanied by vomiting and muscle weakness. Many are interested in the effectiveness of the diet - indeed, a special diet with limited fats and carbohydrates can help reduce symptoms. The question of prognosis often arises - modern methods of supportive therapy can significantly improve the quality of life of patients.
