If both parents are carriers, the chance of the disease is one in four, or 25%, with each pregnancy for an affected child. Genetic counseling and genetic testing are recommended for families who may be carriers of mutations.Each type has been linked to particular mutations. In all, about 80 known GBA gene mutations are grouped into three main types:
Type I (N370S homozygote), the most common, also called the "non-neuropathic" type occurs mainly in Ashkenazi Jews, at 100 times the occurrence in the general populace. The median age at diagnosis is 28 years of age, and life expectancy is mildly decreased. Type II (one or two alleles L444P) is characterized by neurological problems in small children. The enzyme is hardly released into the lysosomes. Prognosis is poor: most die before the age of three. Type III (also one or two copies of L444P, possibly delayed by protective polymorphisms) occurs in Swedish patients from the Norrbotten region. This group develops the disease somewhat later, but most die before their 30th birthday.The Gaucher-causing mutations may have entered the Ashkenazi Jewish gene pool in the early Middle Ages (48–55 generations ago). Pathophysiology
The disease is caused by a defect in the housekeeping gene for lysosomal glucocerebrosidase (also known as beta-glucosidase, EC 3.2.1.45, PDB: 1OGS​) on the first chromosome (1q22). The enzyme is a 55.6-kilodalton, 497-amino acid-long protein that catalyses the breakdown of glucocerebroside, a cell membrane constituent of red and white blood cells. In Gaucher disease, the enzyme is unable to function correctly and glucocerebroside accumulates.
The macrophages that clear these cells are unable to eliminate the waste product, which accumulates in fibrils, and turn into Gaucher cells, which appear on light microscopy to resemble crumpled-up paper.The exact mechanism of neurotoxicity is not understood, but it is thought to involve a reaction to glucosylsphingosine.Different mutations in the GBA (beta-glucosidase) gene determine the remaining activity of the enzyme. In type I, there is some residual activity of the enzyme, accounting for the lack of neuropathology in this type. Although there is some correlation between genotype and phenotype, neither the amount of stored lipids, nor the residual enzyme activity correlates well with disease symptoms. This circumstance has called for alternative explanations accounting for disease symptoms including

jamming of the endo/lysosomal system
ER stress
altered lipid composition of membranes throughout the cell, including the plasma membrane, and consequent changes in the dynamic and signaling properties of the cell membrane
inflammation caused by cytokine secretion as a result of sphingolipid accumulation, and neurodegeneration caused by the accumulation of glucosylsphingosine, a neurotoxinHeterozygotes for particular acid beta-glucosidase mutations carry about a five-fold risk of developing Parkinsons disease, making this the most common known genetic risk factor for Parkinsons.Cancer risk may be increased, particularly myeloma. This is thought to be due to accumulation of glucosylceramide and complex glycosphingolipids.The role of inflammatory processes in Gaucher disease is poorly elucidated. However, sphingolipids are known to participate in inflammation and apoptosis, and markers of macrophage activation are elevated in people with Gaucher disease.