Gaucher's disease

Gaucher disease Wikipedia is the most common type of lysosomal storage disease. It is caused by an enzyme deficiency that affects the liver and spleen as well as other organs. There are 3 clinical subtypes of Gaucher disease, types I, II, and III, with differing symptoms and treatments.

More than 300 mutations are known to occur in the GBA gene, which encodes the enzyme glucosylceramidase. About 1 in 15 Ashkenazi Jews carries a mutation that causes Gaucher disease; the rate in most other populations is much lower. Carriers are not affected; a child born with two copies of the same mutation, however, will develop Gaucher disease. [PMID 17878420]

These SNPs are most commonly associated with Gaucher disease:

• Asn370Ser (also known as N370S) is associated with type I (nonneuropathic) disease
• rs421016 and rs35095275 are associated with types II and III
• Arg463Cys is associated with types II and III
• rs104886460, also known as IVS2+1G-A

23andMe tests for the following SNPs that cause Gaucher disease. These SNPs are also associated with a higher risk of Parkinson's disease.

• rs76763715 or i4000415, also known as N370S (risk genotype CC)
• rs387906315 or i4000417, also known as 84GG (risk genotype GG)
• rs80356773 or i4000386, also known as R496H (risk genotype AA)
• rs80356769 or i4000419, also known as V394L (risk genotype AA)

Gaucher's disease can be treated with an enzyme, but therapy is extremely expensive, and production problems have led to shortages of the drug. [1]

A 2017 publication studying the link between Gaucher disease mutations and Parkinson's disease speculated that Parkinson's may represent a comparatively benign neurologic manifestation of type 1 Gaucher disease, of later onset, while carriers of “severe” mutations (types 2- 4) do not live to develop parkinsonism due to their shorter life spans with other, more malignant neurologic features. These authors also point out in GBA mutation carriers, “severe” mutations have a higher risk of Parkinson's than “mild” mutations (OR: 2.2 [CI 1.5–3.1] vs 13.6 [CI 7.2–25.9]) as well as an earlier onset of symptoms (55.7 vs 57.9 years).10.1186/s40734-017-0054-2