What is Pompe disease?

Pompe disease is a genetic condition characterized by the accumulation of glycogen (a complex carbohydrate) in the lysosomes of cells. The cause of the development of the pathology is a genetic deficiency of the enzyme - acid alpha-glucosidase. The disease is characterized by the wasting and weakness of skeletal and cardiac muscles. Without early diagnostics and treatment, the disease has a fatal outcome.

Two types of Pompe disease have been studied. They are distinguished by the severity of symptoms and the age of the patient when symptoms develop.

Cause of the disease

The cause of Pompe disease is a mutation in the GAA gene. This gene provides the synthesis of the enzyme acid alpha-glucosidase. Acid alpha-glucosidase is involved in the breakdown of glycogen, a complex carbohydrate, into glucose. The enzyme acid alpha-glucosidase is located in the lysosomes of the cell, which are peculiar “processing” organelles and participate in the transformation of various substances and the production of energy from the resulting products.

The mutation in the GAA gene critically reduces the production of the enzyme acid alpha-glucosidase in the body. This leads to a delay in the breakdown of glycogen and its accumulation in the cell's lysosomes, which damages muscle cells and leads to the development of disease symptoms.

The disease is characterized by autosomal recessive inheritance, which means that an affected person must have a mutation in both copies of the GAA gene. One copy is inherited from the mother and the other from the father. Both parents carry the mutation, but they do not develop clinical signs of the disease.

Early (infantile) form of the disease

People who develop symptoms of Pompe disease in childhood tend to have a more severe course of the disease. This form of the disease is characterized by a profound deficiency of the enzyme acid alpha-glucosidase. Symptoms develop from the fourth month of life.

Symptoms include severe muscle weakness, liver enlargement, and heart enlargement due to cardiomyopathy. The disease progresses rapidly. Without treatment, death occurs by 1-2 years of age due to cardiopulmonary failure.

Late (juvenile) form of the disease

Late-onset symptoms can begin at any age, even before the age of 1 year, but without heart enlargement. This is what distinguishes it from early-onset. People with late-onset disease have reduced levels of acid alpha-glucosidase. This form is characterized by moderate severity and a slow rate of disease progression. The earlier the age at which symptoms begin, the more severe the disease.

Symptoms include muscle weakness, which may be complicated by respiratory failure, although this form does not typically develop into cardiomyopathy. Without treatment, a person will develop complications related to respiratory failure.

Epidemiology

Pompe disease is a rare pathology, with an average incidence of 1:40.

Symptoms

Pompe disease is characterized by progressive skeletal muscle weakness. Weakness is particularly pronounced in the lower limbs, upper and lower extremities, and the muscles of the girdle, as well as the diaphragm.

In newborns, it develops:

• Decreased muscle tone – hypotonia
• Cardiomegaly – enlargement of the heart, accompanied by cardiomyopathy
• Hepatomegaly – enlargement of the liver
• Macroglossia – enlargement of the tongue

Other symptoms characteristic of the infantile (early) form of the disease include:

• Weight gain problems and growth retardation
• Difficulty breathing
• Nutritional problems
• Very common respiratory infections
• Hearing loss

In the juvenile (late) form of the disease, symptoms are mild and progress slowly. However, muscle weakness and related complications still dominate the clinical picture.

• Pronounced weakness of the muscles of the limbs and torso
• Difficulty walking (progressive)
• muscle pain
• Motor disorders
• Frequent respiratory infections
• Shortness of breath (dyspnea)
• headache
• severe fatigue
• Unexplained weight loss
• Difficulty swallowing (dysphagia)
• Heart rhythm disorders
• Hearing loss

Diagnosis

Diagnosis of the disease begins with a clinical and family history. Of the clinical and laboratory indicators, the following are important:

• Determination of serum creatine kinase, as it is produced as a result of muscle metabolic processes and an elevated level indicates muscle damage
• Determination of the activity of the enzyme acid alpha-glucosidase in the blood
• Respiratory volume assessment
• Electromyography – to assess the degree of muscle damage
• Cardiological examinations – ECG and cardiac ultrasound

If necessary, genetic testing is performed to determine the mutation. It is also important to conduct carrier screening tests in cases of familial forms of the disease.

Treatment

Treatment for Pompe disease includes enzyme replacement therapy – its delivery as a supplement – ​​and symptomatic treatment.

Because the disease is genetic, it cannot be prevented. Screening for carriers of the mutated gene is important.

Laboratory "Synevo" offers screening for genetic diseases:

Source:

https://my.clevelandclinic.org/health/diseases/5476-fragile-x-syndrome

n.manjaparashvili@synevo.ge