Content

Introduction

Pompe disease, also known as type II glycogenosis, is a rare disease of genetic origin that affects 1 in 10,000 infants and adults. It belongs to the largest group of metabolic diseases from accumulation of lysosomes and is due to the deficiency of an enzyme present within the lysosomes (cell organelles with the task of collecting cell waste and recycling or eliminating them).

The enzyme acid alpha-glucosidase (GAA) or acid maltase present inside the lysosomes, it has the task of breaking down complex sugars, such as glycogen, into simple and digestible sugars such as glucose. The deficiency of this enzyme therefore leads to an accumulation of glycogen inside the cells, especially damaging the cells muscles of the heart, the muscles of the legs and arms and those of breathing.

Symptoms

Pompe disease is classified into two different forms depending on the age at which it presents:

  • classical, or infantile
  • late onset, which occurs in adulthood

The disorders (symptoms) can vary widely in relation to the age at which the disease occurs and its severity.

Infant form

It appears soon after birth and is due to a complete absence of the enzyme acid alpha-glucosidase (GAA).Disorders begin in the first months of life with problems with nutrition, poor weight gain, insufficient ability to suckle milk (difficulty in sucking), muscle weakness, severe enlargement of the heart (hypertrophic cardiomyopathy) and liver. In newborns, the so-called "rag doll posture " due to severe weakness and poor muscle tone (hypotonia), it also causes breathing difficulties and frequent lung infections. Without specific therapy and supportive treatments, newborns with Pompe disease die from heart and / or respiratory failure within the first year of life.

Late onset form

It can occur at any age after the first year of life and its progression is slower, because the lack of the enzyme is partial. The main disorder (symptom) is progressive muscle weakness associated with breathing problems. The heart is usually not involved. The first breathing problems are represented by shortness of breath after physical exertion or, sometimes, headache in the morning and sleepiness during the day (resulting from breathing difficulties during the night). It can lead to a progressive deterioration of the respiratory capacity with recourse often times to assisted pulmonary ventilation (artificial respiration) or tracheostomy (surgical operation that is used to restore respiratory function. It includes a small incision at the neck level into which a small and flexible tube is inserted which creates a passageway for the intended air. lungs).

The worsening of the disease can occur over a longer or shorter time.

Causes

Pompe disease is a genetic disease that is transmitted in a so-called manner autosomal recessive: if both parents carry the defective gene that causes the enzyme deficiency acid maltase, each of them transmits a mutated copy to their child who will have a 25% chance of developing the disease.

There is no gender difference in heredity, meaning men and women are equally likely to get sick.

Diagnosis

The ascertainment of the disease (diagnosis) is based on the finding of the lack of the enzyme (enzyme deficiency) in some blood cells (lymphocytes or fibroblasts). The genetic analysis is carried out through a blood sample and the analysis of the DNA contained in it.

The detection of the disease before birth (prenatal diagnosis) is possible through the measurement of the enzymatic activity on the chorionic villi (part of the placenta that allows the fetus to absorb oxygen and nutrients from the maternal blood and to eliminate waste substances) or through the search for mutations in the cells of the fetus.

Therapy

Pompe disease requires treatment by several specialists: cardiologists, pulmonologists, neurologists, geneticists and also therapists for physical and respiratory therapy in relation to the specific needs of sick people.

Currently, the so-called enzyme replacement therapy. It consists in the administration of the enzyme acid alpha-glucosidase (GAA) missing, intravenously, every two weeks. The enzyme is obtained by biotechnology and is able to replace the missing natural one. The treatment gives excellent results on survival in the infantile form and greatly slows the progression of the disease in the adult or late form.

After several preclinical studies, that is conducted on experimental animals, some clinical trials for the use of gene therapy in people with Pompe disease are underway at an international level.The introduction into the organism - through a viral vector, of copies of healthy genes that produce the GAA enzyme, thanks to bioengineering processes, seems to have highlighted the possibility of reducing the intracellular accumulation of glycogen especially in the nervous system with positive effects on the severity of neurological manifestations. The very preliminary data concerning the results of these experiments indicate that gene therapy could offer greater benefits than enzyme replacement therapy, drastically changing the natural history of the disease, also in terms of frequency and quantity infusions of the replacement enzyme versus gene therapy.

Living with

Pompe disease is a chronic disease that may become more complicated as it develops.

In addition to medical specialists and therapists for physical and respiratory therapy, therefore, psychological support and a discussion with patient associations could be useful to share their experience on how to deal with everyday life.

World Pompe disease day is celebrated every 15 April.

In Italy, Pompe disease is included in the "list of rare diseases for which there is an exemption from the cost of the ticket (Annex 7 of the Prime Ministerial Decree of 12 January 2017), within the" group of "Congenital defects of carbohydrate metabolism and transport"code RCG060.

For information on the disease, the procedure for obtaining the exemption, the clinical diagnosis and treatment centers of the National Rare Diseases Network and patient associations, it is possible to contact the Rare Diseases Toll-Free Telephone (TVMR) 800.89.69.49. The number is active from Monday to Friday from 9.00 to 13.00.

Bibliography

Bembi B, Cerini E, Danesino M A et al. Diagnosis of glycogenosis type II. [Synthesis] Neurology. 2008; 71 (Suppl 2)

Ronzitti G, Collaud F, Laforet P, Mingozzi F. Progress and challenges of gene therapy for Pompe disease. Annals of Translational Medicine. 2019; 7 : 287

Colella P, Mingozzi F. Gene Therapy for Pompe Disease: The Time is now. [Synthesis] Human Gene Therapy. 2019; 30 : 1245-1262

In-depth link

National Institutes of Health (NIH). Genetics Home Reference (GHR). Pompe disease (English)

National Institutes of Health (NIH). Genetic and Rare Diseases Information Center (GARD). Glycogen storage disease type 2 (English)

Italian Glycogenosis Association (AIG). GSD TYPE II - Pompe disease

Association for Glycogen Storage Disease. Type II Glycogen Storage Disease (English)

International Pompe Association (IPA). Pompe disease (English)

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