Respiratory manifestations in hereditary metabolic diseases
Hereditary metabolic diseases (NMDs) are a large group of monogenic, mostly autosomal recessive diseases. They are the result of biochemical disorders, each associated with a specific genetic defect that causes an abnormality of the enzyme involved in the breakdown of the macromolecules of a given chemical substance or their transfer through the cell. The disorder results in a deficiency or abnormal accumulation of undegraded substrate; or an intermediate metabolite, in which a disturbance in the normal functioning of the cells is reached. All organs are affected to varying degrees, including and the lung.
Sir Archibald Garrod described the first of these diseases and proposed the term "inborn errors of metabolism". Today, more than 500 diseases of the group are known, and the number is growing as technology allows the identification of new biochemical and molecular disorders.
The incidence of individual diseases is quite low in the general population, but overall they have a high overall incidence of 1 in 2,500 to 5,000 live births.
Many of the diseases affect the respiratory system, within the framework of the multisystem damage, there are also manifestations that are not directly related to the metabolic disorder. But in all cases, it increases the need for hospitalizations, worsens morbidity, mortality and costs.
In the current study, the attention is focused on the respiratory ones dysfunctions at some NMZs. The rest of the symptomatology is not discussed in detail, the data regarding frequency, epidemiology, biochemical disorders and genetics can be found in the available literature.
The reason for the present presentation is the scanty description of respiratory symptoms, mostly as single case reports or small groups of patients.
At the beginning, the authors of the studies make a general overview of the pathological changes in the body and the respiratory system and the subsequent respiratory symptoms. They dwell on the general principles of diagnosis based on history, physical examination, laboratory and instrumental methods that can be used in these cases. Special attention is given to imaging studies. The treatment of NMZ and their respiratory manifestations - enzyme replacements - is consideredphysical and substrate-reducing therapy, the application of pharmacological chaperones, and the various therapeutic methods used in respiratory system involvement.
The individual nosological units are examined in detail. First of all, lysosomal diseases - acid sphingomyelinase deficiency (Niemann-Pick disease), Gaucher disease, glycogenoses in the face of Pompe disease, mucopolysaccharidoses, Fabry disease, Farber lipogranulomatosis, Hermansky-Pudlak syndrome, Wolman disease . Soco lysinuric protein intolerance has been addressed; such as a violation in the transport and metabolism of amino acids, mitochondrial diseases and the metabolic crisis characteristic of them, some other rare diseases with possible respiratory symptoms - biotinidase deficiency, hereditary orotic aciduria and congenital errors in cobalamin metabolism.
The study is illustrated with 5 clinical observations and also with 7 tables. and 8 fig.
At the end of the presentation, 6 conclusions important for clinical practice are formulated as a conclusion.
The literature reference includes 62 publications, the majority of which are by foreign authors.
