Genetics
The three types of Gaucher's disease are inherited in an autosomal recessive fashion. Both parents must be carriers in order for a child to be affected. If both parents are carriers, there is a one in four, or 25%, chance with each pregnancy for an affected child. Genetic counseling and genetic testing is recommended for families who may be carriers of mutations.
Each type has been linked to particular mutations. In all, there are about 80 known mutations, 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. There are no neurological symptoms.
- Type II (1 or 2 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 3.
- Type III (also 1-2 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.
Diaz et al. suggest that the Gaucher-causing mutations entered the Ashkenazi Jewish gene pool in the early Middle Ages (48-55 generations ago).
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