Gaucher’s Disease in Lithuania: Its Diagnosis and Treatment

Gražina Kleinotienė,Anna Tylki-Szymanska,Barbara Czartoryska

doi:10.3390/medicina47070058

Gražina Kleinotienė, Anna Tylki-Szymanska + Show 1 more

Open Access

https://doi.org/10.3390/medicina47070058

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Abstract

Gaucher's disease is a lysosomal storage disease caused by the lack of beta-glucocerebrosidase enzyme, leading to the accumulation of glucocerebroside. Gaucher's disease is the most frequent type of sphingolipidosis as well as the most frequent lysosomal disease. Clinically, two forms of Gaucher's disease are defined: nonneuronopathic form, so-called type 1, characterized by hepatosplenomegaly, thrombocytopenia, anemia, and osteopenia, and neuronopathic form, known as types 2 and 3, which are also characterized by hepatosplenomegaly, hematological and bone changes; however, involvement of the central nervous system dominates in the clinical picture. Severe deficiency of beta-glucocerebrosidase activity allows confirming the diagnosis based on the clinical picture or the findings of bone marrow examination. Treatment with human glucocerebrosidase was introduced in 1991. Clinically good results are achieved: not only accumulation of glucocerebroside is stopped, but also positive changes in the reticuloendothelial system and an improvement in development and hematological parameters of children are observed as well as the development of bone lesions is reduced. To date, Gaucher's disease has been diagnosed in 8 patients in Lithuania: 3 persons have type 3 and 5 have type 1 disease. Enzyme replacement therapy was started in 2001, and currently 6 persons are being treated. In majority of patients, Gaucher's disease was suspected after exclusion of other possible proliferative diseases. All patients within the first or second year of treatment achieved the therapeutic goals, namely: normalization of hematological parameters, reduction in liver and spleen volumes, and bone pain relief.

Highlights

History Outline Gaucher’s disease is a lysosomal storage disease caused by deficiency in the activity of beta-glucocerebrosidase enzyme leading to the accumulation of glucocerebroside
A deficiency of the lysosomal enzyme beta-glucocerebrosidase, which cleaves glucose from cerebroside under physiological conditions, is the cause of the disease
In two patients (A.V. and D.B.), no foam cells were detected in bone marrow biopsy specimens

Summary

Introduction

History Outline Gaucher’s disease is a lysosomal storage disease caused by deficiency in the activity of beta-glucocerebrosidase enzyme leading to the accumulation of glucocerebroside. Identification of foam cells in bone marrow and characteristic clinical symptoms were the basis of diagnosis of Gaucher’s disease. The symptoms almost always present in adult patients with type 1 Gaucher’s disease are as follows: feeling of exhaustion, weakness, bone pain, increased tendency to bleed (bleeding from the nose, gingiva; subcutaneous effusions, hypermenorrhea), splenomegaly and hepatomegaly; spleen can be enlarged 10 times. It is a quite specific examination for Gaucher’s disease, since in other storage diseases such as Niemann-Pick disease A or B, the chitotriosidase activity level rises but never to such extent Weaker side of this marker is the fact of frequent occurrence of homozygosity for 24-bp mutation in the Caucasian population, which is estimated to be around 6%–12% [6]. Enzymatic therapy is not effective in treatment of neuronopathic form (type 2) of Gaucher’s disease, due to the fact that enzyme does not cross the bloodbrain barrier.

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