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Cystic fibrosis is considered the most common fatal genetic disease of the white race.

It is a monogenic disease and is inherited as an autosomal recessive trait.

Inheritance – Frequency

It is due to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that encodes the corresponding protein.

To date, >2,000 mutations have been identified.

The pathological gene is located on chromosome 7. It is present in one of the two copies of the homologous chromosomes of both parents. They are healthy, simple carriers (heterozygotes).

For the disease to manifest, their child must inherit the gene carrying the mutation from both parents (25% chance), so that both homologous chromosomes are present (homozygote).

In Northern Europe, the frequency of carriers is approximately 4-5% and the frequency of birth of affected newborns is one per 2,000-2,500 births. In our country, with a similar frequency of carriers, approximately 40 patient births are expected each year.

With better knowledge of the pathophysiology of the disease and more aggressive treatment, the survival time of patients from 6-7 years in the 1960s has exceeded 50 years for children born today, mainly due to the more effective treatment of respiratory system problems.

In the coming years, it is expected that survival will increase even further with the widespread application of newer therapies that target the molecular damage of the disease.

Clinical manifestations

The main clinical manifestations of the disease are mainly attributed to a disorder of the transmembrane transport of Cl– ions, resulting in the creation of viscous secretions that lead to airway obstruction and functional insufficiency of the pancreas.

Although the time of onset of symptoms varies, they are usually evident from infancy.

The main manifestations from the lower respiratory tract are recurrent and chronic bacterial infections (staphylococcus, pseudomonas) that lead to permanent lung damage and respiratory function impairment.

The main gastrointestinal manifestation is chronic diarrhea, mainly due to pancreatic insufficiency.

Patients are at increased risk of hypotonic dehydration, especially if exposed to conditions that favor increased sweating, such as during the summer, exercise and fever.

Diagnosis

The diagnosis is based on the clinical picture and the patient’s history (individual, family) and is confirmed by the quantitative determination of chlorides in sweat (sweat test) or the detection of pathological mutations in both chromosomes.

In recent years, a mass screening program for newborns has begun to be implemented in many countries with the aim of diagnosing before the onset of symptoms, from the first days of life. It is now considered a given that early diagnosis results in a better clinical course.

If both parents are proven carriers, prenatal or preimplantation genetic testing is necessary.

Monitoring – Treatment

Patients with cystic fibrosis are regularly monitored in a specialized outpatient clinic, staffed with specialized personnel and appropriate infrastructure.

There is no radical treatment for cystic fibrosis. Treatment is primarily symptomatic and aims to treat problems of the respiratory and digestive systems.

In recent years, with the advent of new therapies that target molecular damage, a significant step has been taken towards controlling the disease.

New innovative etiological therapies aim to repair or enhance the function of the pathological CFTR protein.

Gene therapy is in an earlier phase of development compared to CFTR protein modifiers.