Unit:
ΠΜΣ Μεταβολικά Νοσήματα των ΟστώνLibrary of the School of Health Sciences
Author:
Koutsostathis Efstathios
Supervisors info:
Λυρίτης Γεώργιος, Ομότιμος Καθηγητής, Ιατρική, ΕΚΠΑ
Δοντά Ισμήνη-Νίκη, Καθηγήτρια, Ιατρική, ΕΚΠΑ
Τριανταφυλλόπουλος Ιωάννης, Επίκουρος Καθηγητής, Ιατρική, ΕΚΠΑ
Original Title:
Νόσος του Gaucher και μεταβολικά νοσήματα των οστών
Translated title:
Gaucher disease and metabolic bone diseases
Summary:
Gaucher disease, the most common of the lysosomal storage diseases,results from mutations in the chromosomal region 1q21, that encodes the glucocerebrosidase gene. The impairment of the enzymatic activity of β-glucocerebosidase leads to the accumulation of glucocerebroside, its substrate, in the lysosomes of the macrophage/monocyte system. The macrophages are transformed to atypical activated cells that infiltrate various organs and also secrete pro-inflammatory cytokines, leading to a chronic inflammatory phenotype.
There are three types of Gaucher disease:
• Type 1 is the most common. It is characterized by internal organ and osseous involvement, without manifestations from the nervous system.
• Type 2 manifests early at infancy, it is characterized by intense CNS involvement with life expectancy about 2 years.
• Type 3 has less severe CNS involvement and better life expectancy (adulthood).
The osseous manifestations are very common in type 1 and include osteopenia, osteoporosis, painful bone crisis, fractures, osteonecrosis and Erlenmeyer flask deformity. The accumulation of the glucocerebroside in the lysosomes of the macrophages along with the secretion of chemokines affect the function of both the osteoblasts and the osteoclasts and lead to the previously mentioned clinical and radiographic manifestations.
The treatment of the disease includes β-glucocerebosidase substitution therapy. Recently, new approaches involving gene therapy have evolved.
The issues and challenges regarding Gaucher disease involve the genetic heterogeneity, the multi-organ involvement, the effects of the disease in the macrophages and the development of effective treatments, especially for the neuronopathic types.
Main subject category:
Health Sciences
Keywords:
Lysosomal storage disease, Gaucher disease, Macrophages, β-glucoserebrosidase, Osseous disease
