Gaucher (pronounced "go-SHAY") disease is an inherited illness caused by a gene mutation. Normally, this gene is responsible for an enzyme called glucocerebrosidase that the body needs to break down a particular kind of fat called glucocerebroside. In people with Gaucher disease, the body is not able to properly produce this enzyme, and the fat can not be broken down. It thenaccumulates, mostly in the liver, spleen, and bone marrow. Gaucher disease can result in pain, fatigue, jaundice, bone damage, anemia, and even death.
Gaucher disease is considerably more common in the descendants of Jewish people from Eastern Europe (Ashkenazi), although individuals from any ethnic group may be affected. Among the Ashkenazi Jewish population, Gaucher disease is the most commongenetic disorder, with an incidence of approximately 1 in 450 persons. In the general public, Gaucher disease affects approximately 1 in 100,000 persons. According to the National Gaucher Foundation, 2500 Americans suffer from Gaucher disease.
In 1991, enzyme replacement therapy became available as the first effective treatment for Gaucher disease. The treatment consists of a modified form ofthe glucocerebrosidase enzyme given intravenously. Performed on an outpatient basis, the treatment takes about 1-2 h and is given every 2 weeks. Enzyme replacement therapy can stop and often reverse the symptoms of Gaucher disease, allowing patients to enjoy a better quality of life.
Charcot-Marie-Tooth disease (CMT) is named after its three discoverers, who firstnoted the disease around the turn of the century. It is the most common inherited peripheral neuropathy in the world, characterized by a slowly progressive degeneration of the muscles in the foot, lower leg, hand, and forearm and a mild loss of sensation in the limbs, fingers, and toes. Full expression of CMT's clinical symptoms generally occurs by age 30. CMT is not a fatal disease, however, andthe disorder does not affect normal life expectancy.
CMT is a genetically heterogeneous disorder in which mutations in different genes can produce the same clinical symptoms. In CMT there are not only different genes but different patterns of inheritance. One of the most common forms of CMT is Type 1A. The gene for Type 1A CMT maps to chromosome 17 and is thought to code for a protein (PMP22)involved in coating peripheral nerves with myelin, a fatty sheath that is important for their conductance. Other types of CMT include Type 1B, autosomal-recessive, and X-linked.
The same proteins involved in the Type 1A and Type 1B CMT are also involved in a disease called Dejerine-Sottas Syndrome (DSS), in which similar clinical symptoms are presented, but they are more severe. Research intounderstanding the pathogenesis of CMT, through the use of animal models for the disease, should also give insight into DSS and may lead to therapies for both diseases.
Edward Alfred Cockayne (1880-1956), after whom this disease is named, was a London physician who concentrated particularly on hereditary diseases of children. Cockayne syndrome is a rare inherited disorder inwhich people are sensitive to sunlight, have short stature, and have the appearance of premature aging. In the classical form of Cockayne syndrome (Type I), the symptoms are progressive and typically become apparent after the age of 1 year. An early onset or congenital form of Cockayne syndrome (Type II) is apparent at birth. Interestingly, unlike other DNA repair diseases, Cockayne syndrome isnot linked to cancer.
After exposure to UV radiation (found in sunlight), people with Cockayne syndrome can no longer perform a certain type of DNA repair, known as "transcription-coupled repair." This type of DNA repair occurs "on the fly" right as the DNA that codes for proteins is being replicated. Two genes defective in Cockayne syndrome, CSA and CSB, have been identified so far. The CSA...