Gaucher Disease.pptx

Gaucher Disease

1. Ade Wijaya , MD – November 2022 Gaucher Disease

2. Introduction Synonyms: Glucocerebrosidase Deficiency Glucosylceramidase Deficiency

3. Classification GD type 1  is characterized by the presence of clinical or radiographic evidence of bone disease ( osteopenia , focal lytic or sclerotic lesions, and osteonecrosis ), hepatosplenomegaly , anemia and thrombocytopenia, lung disease, and the absence of primary central nervous system disease. GD types 2 and 3  are characterized by the presence of primary neurologic disease; in the past, they were distinguished by age of onset and rate of disease progression, but these distinctions are not absolute. Disease with onset before age two years, limited psychomotor development, and a rapidly progressive course with death by age two to four years is classified as GD type 2. Individuals with GD type 3 may have onset before age two years, but often have a more slowly progressive course, with survival into the third or fourth decade.

4. Classification The  perinatal -lethal form  is associated with ichthyosiform or collodion skin abnormalities or with nonimmune hydrops fetalis . The  cardiovascular form  is characterized by calcification of the aortic and mitral valves, mild splenomegaly , corneal opacities, and supranuclear ophthalmoplegia . Cardiopulmonary complications have been described with all the clinical subtypes, although varying in frequency and severity.

5. Diagnosis The diagnosis of GD relies on demonstration of deficient glucocerebrosidase ( glucosylceramidase ) enzyme activity in peripheral blood leukocytes or other nucleated cells or by the identification of biallelic pathogenic variants in  GBA .

6. Differential Diagnosis Saposin C deficiency or prosaposin deficiency Lysosomal storage diseases (LSDs ) Hepatosplenomegaly  is observed in Niemann -Pick disease types A and B (see  Acid Sphingomyelinase Deficiency ),   Niemann -Pick disease type C ,   Wolman disease ( lysosomal lipase deficiency), the mucopolysaccharidoses (including  mucopolysaccharidosis type I and   mucopolysaccharidosis type II , and the oligosaccharidoses . Legg- Calvé - Perthes disease  Gaucher cells Congenital ichthyoses and collodion skin changes  Hydrops fetalis Myoclonic seizures

7. Management Treatment of manifestations Prevention of primary manifestations: enzyme replacement therapy (ERT) or substrate reduction therapy (SRT ) Prevention of secondary complications Surveillance Agents/circumstances to avoid : Nonsteroidal anti-inflammatory drugs in individuals with moderate to severe thrombocytopenia . Evaluation of relatives at risk Pregnancy management :  Genetic counseling

8. Summary Glucocerebrosidase ( glucosylceramidase ) enzyme deficiency in peripheral blood leukocytes or other nucleated cells Type 1 in adult but no neurological symptoms Type 2 in infancy Type 3; onset in infancy but slowly progressive into adults Multidisciplinary approach Treatment of manifestations Enzyme replacement therapy (ERT) or substrate reduction therapy (SRT) Genetic counseling

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