Pompe disease: Tips and recommendations.

It is estimated that one in every 138,000 live births suffers from it and in its adult form it has an incidence of one in every 57,000 people.

How is it produced?

Lysosomes are parts of cells that accumulate in their interior a series of enzymes that digest substances outside the cell to obtain benefit from them or degrade them, such as glucose. One of the enzymes found inside these organelles is acid alpha-1,4-glucosidase, which is responsible for breaking down glycogen, a chain of multiple glucose molecules, into loose units that can be used by the cell and accumulate in the lysosome. In Pompe disease there is a genetic alteration that leads to a deficiency of this enzyme. The gene that codes for this enzyme is the GAA gene and it is located on chromosome 17, specifically in the 17q23 region. This genetic alteration is inherited in an autosomal recessive manner, that is, it is necessary that both copies of the GAA gene are altered for the disease to manifest itself.

As there is little or no presence of this enzyme, glycogen accumulates in the lysosomes without being degraded, the lysosomes grow and alter the normal functioning of the cells and consequently of the tissue and organs where they are found.

Pompe disease has two forms, one childhood, in which practically the presence of the enzyme is less than 1%, and the adult form, which occurs later and with some presence of the enzyme, around 40 % of what would be normal in healthy individuals.

Symptoms

In the infantile form of Pompe disease, symptoms appear before three months of age and there is a high risk of death during the first two years of life. 96% of affected children have low muscle tone (hypotonia), they look like rag dolls that cannot hold their head up or maintain an erect position. The facial muscles of these children are flabby, so that their faces are not very expressive.

They have difficulties with sucking, the tongues are often large (in 62% of the cases), due to the accumulation of glycogen in the muscle cells of the tongue, which can lead to them not gaining weight due to not being able to feed properly. Likewise, these children tend to have respiratory problems due to involvement of the intercostal muscles, an increase in liver size in 82% of cases, and decreased or completely abolished tendon reflexes.

Due to the excessive accumulation of glycogen in the lysosomes of cardiac cells, the muscular walls of the heart grow in size excessively, making it difficult for the organ to carry out its function of pumping blood correctly: this is what is called cardiomegaly, a heart big. This fact occurs in 95% of patients with infantile Pompe disease and is the one that most limits their good prognosis.

When the disease manifests itself in adulthood it is because there is some activity of the acid alpha-1,4-glucosidase enzyme, so that symptoms do not appear until it is exhausted. The more enzyme activity there is, the later the symptoms will begin and, conversely, the earlier the symptoms occur, the worse the prognosis.

In adults the clinic usually begins as a difficulty in walking, climbing stairs and standing. The weakness they notice is mainly at the level of the lower extremities and the trunk, generally respecting the arms and neck. These patients, as in the infantile form, have low muscle tone, as well as diminished reflexes.

The affectation of the back muscles leads to alterations of the spine in the form of lordosis or, which usually causes low back pain or back pain.

The involvement of the respiratory muscles causes these patients to progressively acquire difficulty in breathing (dyspnea), eventually becoming necessary artificial oxygen supply. These patients present orthopnea, increased respiratory distress when lying down, and must sleep with several pillows or even sitting up. respiratory distress makes them unable to expel the bronchial secretions properly, which accumulate and can often become infected, leading to severe or severe.

In the long run, these patients may also have difficulty chewing and swallowing food, which further weakens them. Like children, they may have hepatomegaly, an enlargement of the liver.

In none of the cases, neither in children nor in adults, is intellectual abilities affected.

Diagnosis

The diagnosis in childhood will begin with the aforementioned clinic, seeing children who are not able to suck correctly, do not gain weight and especially with low muscle tone and partial or total absence of reflexes.

In those, it can be observed that a cardiac enzyme, creatine kinase (CK), is elevated up to 10 times above normal values, with the rest of the normal blood test, without affecting liver function despite the increase in liver size.

It is advisable to perform a chest X-ray where, in general, the increase in the size of the heart can already be appreciated. To complete the study, an ultrasound of the heart must be performed, as well as an ultrasound that will provide more information about its size and function. Likewise, an abdominal ultrasound will make it possible to assess the increase in liver size.

The definitive diagnosis will be given by the determination of acid alpha-1,4-glucosidase levels in a biopsy of either skin fibroblasts, muscle cells, or white blood cells.

In the adult form, the same tests will be carried out, knowing that the CK may not be elevated. Electrophysiological studies can be performed to assess the muscular and nervous function of the affected areas.

Treatment

The essential treatment of this disease is to control the symptoms that can lead to cardiac, muscular and respiratory disorders, sometimes requiring the use of oxygen therapy or mobility aids in adults.

There is a synthetic enzyme, alglucosidase alpha, marketed under the name Myozyme®, which makes up for the lack of acidic alpha-1,4-glucosidase. This drug should be administered every two weeks and adjusted for weight, at a rate of 20 mg for each kilo of weight. The biggest problem with this medication, beyond having to administer it every two weeks and for life, is its high cost, since a vial of about 50 mg of the enzyme costs almost 600 euros.

Precautionary measures

Pompe disease is a congenital disease and therefore there are no preventive measures against it. If you suspect it, it is essential to put yourself in the hands of the specialist as soon as possible.

• This disease mainly affects the muscles and the heart, affecting their functioning.
• It has an infantile form (it appears before the age of three) and an adult form (the first symptom is difficulty walking and standing up).
• Essential treatment is based on controlling symptoms.