What is Subacute Necrotizing Encephalopathy & How is it Treated?

Subacute Necrotizing Encephalopathy which is also known by the name of Leigh Syndrome is an extremely rare genetic condition which is characterized by gradual degeneration of the central nervous system meaning that there is gradual and progressive deterioration in function of the brain, spinal cord, and the optic nerves.

The early symptoms of Subacute Necrotizing Encephalopathy may present themselves by the time the child is three months of age and progress gradually. In some cases, symptoms of Subacute Necrotizing Encephalopathy may not appear until the child is two to three years of age or even more.

The first presenting symptom of Subacute Necrotizing Encephalopathy is gradual deterioration of the neurological functioning of the child with psychomotor retardation where the child tends to lose the previously acquired motor skills before the onset of symptoms.

Additionally, he child suffering from Subacute Necrotizing Encephalopathy will lose interest in eating due to poor appetite and as the disease condition advances the child starts to experience bouts of seizures, generalized weakness, hypotonia, and most importantly lactic acidosis which tends to impair the kidney and respiratory function.

The root cause of Subacute Necrotizing Encephalopathy is a deficiency in the mitochondrial enzymes which is responsible for energy production namely enzymes of mitochondrial respiratory chain complex or the pyruvate dehydrogenase complex.

Subacute Necrotizing Encephalopathy is an autosomal recessive disorder meaning that two copies of the defective gene from each parent is required for the development of Subacute Necrotizing Encephalopathy.

As stated above, the root cause for Subacute Necrotizing Encephalopathy is the deficiency of enzymes responsible for energy production namely the mitochondrial respiratory chain enzymes or the enzyme components of the pyruvate dehydrogenase complex.

The main reason for the deficiency of these enzymes is mutations in certain genes. The mutations of these defective genes are also termed as genetic heterogenicity. Subacute Necrotizing Encephalopathy follows an autosomal recessive trait meaning that copies of the defective gene one from each parent is required for a child to inherit Subacute Necrotizing Encephalopathy, although there have been some cases where no genetic cause has been found for the development of Subacute Necrotizing Encephalopathy.

In Subacute Necrotizing Encephalopathy, the genetic mutations in mitochondrial DNA start to interfere with the energy sources in the brain cells which are responsible for motor function. As a result of this interference, there is impairment in the ability of the cells to perform their functions fully resulting in gradual degeneration of the brain cells resulting in development of Subacute Necrotizing Encephalopathy.

The symptoms of Subacute Necrotizing Encephalopathy normally start by the time the child reaches the third month of life although in some cases symptoms may not appear even after the child reaches 2 to 3 years of age but once the symptoms appear they tend to progress rapidly.

The first sign of Subacute Necrotizing Encephalopathy is the loss of the ability of the child to suck or what is called as a poor suck response. This is then followed by loss of motor skills and head control.

As the condition advances, there is gradual loss of appetite, persistent vomiting, and neurological disorders in the form of seizures and loss of muscle tone or hypotonia. The most important symptom of Subacute Necrotizing Encephalopathy is the development of lactic acidosis which results in respiratory and kidney abnormalities which may lead to potentially serious complications.

There are various tests available which can confirm the diagnosis of Subacute Necrotizing Encephalopathy. The diagnosis starts with a clinical evaluation of the patient and history taking to determine as to when the symptoms started and the severity of the symptoms.

The physician will also inquire about any regression of milestones that the child may have achieved before the onset of symptoms. Once Subacute Necrotizing Encephalopathy is suspected, then advanced radiological studies of the brain will be recommended which in cases of Subacute Necrotizing Encephalopathy will clearly show abnormalities in certain areas of the brain like the basal ganglia or brainstem. This will further fortify a diagnosis of Subacute Necrotizing Encephalopathy.

Laboratory investigations and blood studies will confirm the presence of lactic acidosis which is a classic sign of Subacute Necrotizing Encephalopathy. An enzyme assay will be then done which will clearly show a deficiency in the enzymes pyruvate dehydrogenase complex confirming the diagnosis of Subacute Necrotizing Encephalopathy.

There is no clear cut treatment for Subacute Necrotizing Encephalopathy and treatment is purely supportive and symptomatic. The treatment for this condition requires a multidisciplinary approach from different specialties including pediatricians, neurologists, cardiologists, neurosurgeons, physical and occupational therapists.

The most preferred treatment for Subacute Necrotizing Encephalopathy by far is thiamine administration. This may provide temporary improvement in symptoms and may slow down the progression of disease process.

Additionally, since Subacute Necrotizing Encephalopathy is caused due to a deficiency in pyruvate dehydrogenase enzyme complex, thus a diet rich in fat and low carbohydrate may also be recommended as an option to treat some of the symptoms of Subacute Necrotizing Encephalopathy.

Physical and occupational therapy may also be useful for strengthening the muscles and improving the tone of the muscles. Apart from this, only supportive treatment is available for Subacute Necrotizing Encephalopathy.

Unfortunately, the overall prognosis for children with Subacute Necrotizing Encephalopathy is extremely poor. Children who have deficiency in pyruvate dehydrogenase deficiency and have impaired mitochondrial complex IV usually succumb within three to four years as a result of Subacute Necrotizing Encephalopathy.