What to Know About Alper’s Disease?

Alpers-Huttenlocher syndrome

Alpers disease, also known as Alpers-Huttenlocher syndrome, refers to the loss of key enzymes in mitochondrial DNA. It is a type of autosomal recessive disorder caused by a mutation in the POLG1 gene which is responsible for producing mitochondrial DNA polymerase gamma (pol γ). These mutations impair the protein's ability to replicate mitochondrial DNA (mtDNA), leading to reduced mtDNA levels in cells. This dysfunction causes a significant energy deficit in the cells, particularly in the high-energy demanding brain and liver, resulting in the progressive symptoms characteristic of the disease.

Before the advancement of next-generation sequencing, diagnosing patients with gene mutations or mitochondrial disease was difficult. The reason being, similarities in symptoms like cardiovascular disorders, neurodegenerative disorders, cancer, obesity and neurometabolic diseases.

What is Alpers disease?

The rare genetic disorder of Alpers disease causes health conditions like seizures, liver failure and dementia. Scientists believe this type of disorder happens because of the mitochondria’s abnormality. Only 1 in a million suffers from Alpers disease.  

Mitochondria are the powerhouses of a cell that generate around 90% of the energy a human body needs to function. When mitochondria are unable to function properly, it causes muscular and neurological damage. Children within the age range of 2 to 4 or 17 to 24 are more prone to such conditions.

Alpers Disease has multiple names:

• Alpers progressive infantile poliodystrophy
• Progressive cerebral poliodystrophy
• Poliodystrophy cerebral progressive
• Alpers progressive sclerosing ppoliodystrophy
• Alpers syndrome
• Alpers-Huttenlocher syndrome

What are the symptoms of Alpers disease?

The following are some significant symptoms of early Alpers disease:

1. Seizures or refractory epilepsy
2. Gradual onset of cognitive impairment
3. Liver disease
4. Brain disease
5. Low blood sugar or hypoglycaemia
6. Migraine or headache
7. Muscle stiffness and twitching
8. Depression and anxiety
    

As Alpers disease progresses, a new set of symptoms occurs, which are as follows:

1. Dementia
2. Gastrointestinal disease
3. Dysphagia, or difficulty swallowing
4. Blindness
5. Ataxia, or difficulty in movements
6. Liver cirrhosis or failure
7. Progressive ataxia and spasticityor loss of limb control
    

What are the Causes of Alpers Disease?

A mutation in genetics is the central cause of Alpers disease. If there is a mutation in the POLG1 gene, it can lead to Alpers disease. POLG1 is responsible for encoding the mitochondrial DNA polymerase, which replicates the genome.

When there is a mutation, POLG faces depletion and causes mitochondrial disorders like Alpers disease. Researchers have found that there are ~1% of people in the Europe with the POLG mutation. Both parents can pass these mutations to their children.

Alpers Syndrome and Genetics

Alpers-Huttenlocher syndrome is a genetic condition in which mutation in POLG1 gene result into this disease. This mutation minimizes the effectiveness of polymerase gamma which is a significant part of mitochondrial DNA. Alpers disease can be inherited in an autosomal recessive pattern. A person can develop an autosomal recessive condition if they inherit the mutated gene from each parent. There is also more than one type of gene mutation that can cause the disease.

People can inherit Alpers disease is an autosomal recessive pattern. An individual can develop an autosomal recessive medical condition if they inherited the mutated gene from both parents. There is also more than one type of gene mutation can cause the disease.

A person can inherit a POLG1 mutation from two ways:

• Homozygous: Means an individual has two identical mutations (alleles) in the POLG gene, one inherited from each parent.
• Heterozygous: Means an individual has two different mutations in the POLG gene, one on each allele.
   

The specific mutations involved, rather than whether they are homozygous or heterozygous, are the primary determinant of the disease's severity and age of onset. Certain mutations are associated with earlier onset (infancy to early childhood), while others may present later in childhood or adolescence.

Organs Affected by Alpers Disease

The brain and liver are among the most severely affected organs due to their exceptionally high energy demands. Therefore, energy deficiency in these organs results into a range of severe symptoms, including seizures, liver failure, and development regression.

Does it Affect an individual’s Life Expectancy?

Alpers syndrome significantly reduces a person’s life span. In most of the medical cases, persons do not live past their first decade. An individual life expectancy may be lesser than 4 years after the initial onset of symptoms. Moreover, common causes of death are liver failure and brain dysfunction.

How is Alpers Disease Diagnosed?

The main symptoms of dementia or seizure indicate to healthcare providers the possibility of Alpers disease. Then, they conduct tests like electroencephalography (EEG), cerebrospinal fluid analysis, genetic testing and MRIs to confirm.

How Is Alpers Disease Treated?

As of now, there is no permanent treatment for Alpers disease. However, some therapies and medications help manage the symptoms. They are as follows:

1. Muscle massage to decrease stress
2. Anticonvulsant medications that help with the seizure episodes
3. Feeding tubes for patients who are struggling with swallowing or eating
4. Muscle relaxants or pain relievers
5. Speech therapy
6. Occupational therapy teaches patients how to perform daily routine tasks.
    

Alper's disease starts with one or two symptoms. However, it worsens over time. Plus, it has a poor mortality rate. Therefore, monitoring the symptoms and being in contact with a professional health expert at all times is necessary. Children with Alpers disease often suffer from nutritional and gastrointestinal issues and psychological issues. The parents need to keep an eye on these issues and appoint palliative care whenever needed.

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