IllnessCYP2D6 in the context of planned therapy for M. Gaucher

Sanger

Gaucher disease patients do not produce enough glucocerebrosidase, so glucocerebrosides accumulate in so-called Gaucher cells in the liver, spleen, lungs and bone marrow. Bone damage can be particularly painful; in rare cases Gaucher cells can also accumulate in the brain and lead to the more severe form of the disease. Three forms of Gaucher disease are distinguished. Type 1 is the most common form in the western world (90%), usually with a normal lifespan. Symptoms can start at any age with anaemia, bruising, bleeding, pain and growth disturbances. Type 2 disease is very rare and characterised by damage to the central nervous system, which is usually fatal in the first two to four years of life. Although type 2 occurs worldwide, it is very rare. Type 3 is rare in the West, more common in Asia and in a province of Sweden. In this type, the neurological symptoms develop slowly, usually in childhood, and continue into adulthood. Gaucher disease is transmitted autosomal recessively. Virtually all sequence changes in the GBA gene are point mutations that can be fully detected.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1269/

 

90% type 1 cases are eligible for Cerdelga therapy unless there is an ultra-fast YP2D6 metaboliser type or an unclear status of metabolism.

 

• Allelic: Codeine sensitivity
• Allelic: Debrisoquine sensitivity
• Cerdelga-Therapie - Morbus Gaucher
• Cytochrom P450 2D6
• Fremdsubstanz-Metabolisierer (Opiode, trizyklische Antidepressiva, Neuroleptika, Beta-Blocker etc.)
• Poor and/or ultrarapid metabolism of several drugs, including debrisoquine, sparteine, nortriptyline