Alpers’ Disease: Diagnosis and Treatment

Alpers disease is a rare mitochondrial disease. As a rule, you can diagnose it with a genetic or blood test. It manifests as a progressive encephalopathy combined with cirrhosis of the liver.

The molecular basis of the disease is a gamma polymerase deficiency. It is the only eukaryotic DNA polymerase. It supports DNA replication in the mitochondria. One of the well-known facts of Alpers’ disease is that the level of replication of genetic material is critically low. While mitochondrial enzyme activity is impaired. ATP deficiency affects the most energy-dependent structures:

• the central and peripheral nervous system;
• liver;
• gastrointestinal organs. 

Alpers’ disease manifests in infancy through sudden seizures. They can be general or local. There are no apparent signs of liver damage. As you get older, more and more symptoms can appear. Scientists have observed some changes in liver biochemical tests. The following symptoms are:

• delayed psychomotor and physical development;
• muscle hypotonia;
• impaired coordination of movements. 

The syndrome was first described by Alphonse Maria Jacob. He is the teacher of the American neurosurgeon Bernard Jacob Alpers. Bernard published the findings of his mentor in 1931.

Alpers’ Syndrome Diagnosis

At the initial appointment, the neurologist, identifies atypical epileptic encephalopathy. This requires mandatory confirmation or exclusion of Alpers disease. A geneticist, hepatologist, and cardiologist take part in the examination of the patient. They take into account the polymorphism of clinical manifestations. Then doctors prescribe instrumental, and laboratory examination methods to verify the diagnosis:

EEG

In the beginning, the doctor determines:

1. Bipolar epileptic activity;
2. Homolateral epileptic activity. 

This activity exists in the form of spikes and polyspikes. Diffuse slow activity is characteristic of the period of Alpers’ disease onset. It occurs in occipital areas with accents in temporoparietal areas of the brain. Diagnosis allows the physician to assess the features of brain fluctuations. The physician can also detect the presence of abnormalities in this process.

MRI of the Brain

The images show areas of the moderately hyperintense signal. They are visible in the occipital areas of the cerebral cortex. The appearance of areas of increased intensity characterizes sustained seizures. Doctors detect them in the thalamus and medulla oblongata. Progressive atrophy during Alpers’ syndrome diagnosis is evident in:

1. Basal ganglia;
2. Brainstem;
3. Cerebellum.

Abdominal Ultrasound Examination

In toxic hepatitis, there is:

1. Moderate liver enlargement;
2. Decreased echogenicity of its parenchyma. 

To clarify the nature of the pathology, the doctor performs an organ biopsy. Its results reveal:

1. Fatty infiltration of hepatocytes;
2. Proliferation of bile ducts;
3. Liver fibrosis (in case of long-term existence of the disease). 

The method helps to assess the presence of dead liver cells and the viability of the internal organ.

Blood Tests

To make Alpers’ syndrome diagnosis  with a biochemical blood test, the doctor determines:

1. Hypoglycemia;
2. Elevated levels of transaminases;
3. Hyperbilirubinemia;
4. Hyperammonemia;
5. Hypoalbuminemia. 

They show the development of liver failure. The doctor evaluates a correlogram when the prothrombin index is low. The study reveals high content of hepatic enzymes in the biological fluid.

Genetic Analysis

Doctors use it to detect a chromosomal mutation. It is one of the facts of Alpers’ disease. All children with suspected Alpers’ syndrome need a complete analysis of the gene. The doctor does this by direct automated sequencing.

The frequent mutation test is a screening test for the most common cases. Professionals perform this test in the mitochondrial polymerase gamma gene. Verification of the diagnosis is possible if the physician detects the mutation.

In general, we know  60 types of mutations. Several points make gene sequencing the most informative method of confirming a diagnosis: 

1. A large number of mutations;
2. A lack of specific biochemical markers for gamma polymerase.

Sometimes doctors supplement the test by measuring the number of copies of DNA.

Computed Tomography (CT) Scan

Diagnostic scans are among the most informative Alpers’ disease examination methods. It helps to identify foci of destruction. It also makes a prognosis about a person’s impending deterioration.

Treatment of Alpers Disease  

Alpers Disease is incurable, and treatment focuses on managing the symptoms. Treatment with anti-epileptic medication reduces the frequency and severity of seizures. Often, an individual’s healthcare team will adjust the dosage to find an effective balance between seizure control and side effects. 

Other treatments can include physical and occupational therapy or speech therapy. They help improve physical functioning, learning ability, communication, and coordination. Also, doctors can prescribe vitamins that contain coenzyme Q10. They help prevent liver damage. They can also lessen the severity of symptoms associated with liver failure.

Besides medical treatment, caregivers need to provide emotional support and a safe environment. It allows the individual with Alpers disease to live as comfortably as possible. This can include helping to maintain a consistent routine. It can also provide a calming environment with minimal stress.

Conservative Therapy

The difficulty in providing medical care to Alpers’ disease sufferers is the lack of effective etiopathogenetic medications. The treating physician selects symptomatic therapy individually for the patient. It corrects neurological disorders and stabilizes homeostasis parameters. Professionals carry out the treatment in neurological or intensive care units. As a rule, doctors recommend using the following medicines:

• Antioxidants. They are from the group of vitamin-like substances. They have a positive anabolic effect and improve metabolic parameters. They are the only drugs that allow for stopping valproate-induced liver failure.

• Anticonvulsants. Most physicians recommend modern anticonvulsants for the management of epileptic seizures. Doctors recommend using them from the groups of sulfate-substituted monosaccharides and lamotrigine. Since they do not cause toxic hepatitis during Alpers’ disease treatment. If they are ineffective, patients use older drugs (barbiturates, benzodiazepines).

• Infusion solutions. For correction of water-electrolyte, exchange doctors prescribe crystalloid solutions. They can also administer infusions of glucose preparations and amino acid mixtures. It is necessary to maintain an adequate level of energy metabolism.

Palliative Care

In some cases, a technique known as palliative care can help manage symptoms. It can also reduce pain and suffering. This Alpers’ disease treatment includes:

• intravenous hydration;
• administration of nutrient mixtures;
• relief of seizures;
• elimination of hypoxia by hyperbaric oxygenation; 
• oxygen support;
• artificial ventilation. 

Palliative care includes social and psychological care for the patient’s family members.

Alpers’ Disease Prognosis

The prognosis for recovery from Alpers syndrome is unfavorable. The syndrome is accompanied by joint stiffness and chest deformity in newborn children. Doctors also note the unnaturally small body weight of the child. Signs of the disease tend to progress constantly. But, with timely treatment, the patient can relieve the symptoms to maintain a stable condition. 

Alpers Disease Life Expectancy

According to the literature, children, die within four years after the onset of the disease. The use of valproic acid to relieve epileptic seizures catastrophically increases the progression of the disease. It can cause the rapid development of fatal toxic hepatitis. 

In the case of atypical epileptic encephalopathy in a child, it is necessary to exclude the Alpers-Huttenlocher syndrome. You should also avoid prescribing valproic acid until the diagnosis is clarified. As a rule, the prognosis of  Alpers’ disease life expectancy is quite wrong. Doctors can make the diagnosis with mandatory genetic testing for the POLG gene.

A Word from Lone Star Neurology Professionals 

Statistically, most patients in their young years have a bad prognosis from this rare genetic disorder.  However, timely diagnosis of Alpers’ syndrome  with prescription of supportive therapy and exclusion of valproic acid drugs from treating epileptic seizures can reliably increase the patient’s life expectancy. You can always consult our Lone Star Neurology professionals for more information.

FAQs 

• Is Alpers’ syndrome genetic?

It is a hereditary disease with an autosomal recessive transmission mechanism. It is characterized by blindness, localized or generalized seizures, myoclonic manifestations, and dementia. 

• What causes Alpers-Huttenlocher syndrome?

The mutations responsible for the brain’s mitochondria cannot work correctly. Also, people cannot perform their basic functions. The cells gradually lose the ability to expend the energy the human body receives in the process of assimilation of nutrients.

• What is Alpers’ syndrome?

It is a hereditary disease. It refers to a group of diseases associated with impaired mitochondrial function. It leads to impaired energy functions in the body. Delayed psychomotor development and epileptic seizures are also common. A widespread occurrence is liver damage due to medication.

• When is the greatest risk of getting Alpers’ syndrome?

The greatest risk of developing the disease is when both parents are recessive carriers of the genetic mutation. Having a defective chromosome in one parent minimizes the likelihood of Alpers syndrome.