Cystic Fibrosis

Cystic fibrosis

Gaucher disease Type I is a disorder caused by a lack of glucocerebrosidase, an enzyme that helps clear glucocerebroside from cellular structures called lysosomes. The condition can lead to slower growth in children, bone degeneration, anemia, enlargement of the spleen and liver, and thrombocytopenia. A replacement enzyme treatment is available, but the product is expensive-in excess of $100,000 per patient annually. The carrier rate among the Ashkenazi is between one in 10 and one in 15. Not everyone who inherits two Gaucher disease mutations develops the disease or is aware of it.

Tay-Sachs disease is characterized by absence of hexosaminidase A, an enzyme that breaks down GM2-ganglioside. Without this enzyme, fat builds up in the central nervous system, leading to neurological degeneration. Afflicted children become symptomatic at around six months, and the disease is usually fatal in children within a few years. (Adult-onset forms of Tay-Sachs disease are rarer and less severe.) Carrier screening can be done on a blood sample looking at DNA mutations or enzyme levels, since carriers have reduced levels. A combination of enzyme level and mutation studies is the most accurate test. The carrier rate among the Ashkenazi Jewish population is about one in 25; the rate is about one in 50 among French Canadians, Cajuns and Irish.

Other conditions with a higher carrier rate in the Ashkenazi Jewish population for which testing is available include:

• Bloom syndrome, a chromosome breakage disorder. Symptoms include growth retardation, skin discoloration and typical facial features. The disease often leads to cancer and sometimes mental retardation. The carrier rate among Ashkenazis is about one in 100.
• Familial Dysautonomia is a disease that causes the autonomic and sensory nervous system to malfunction. Symptoms include the absence of tears, taste buds, and deep-tendon reflexes. The gene was recently identified and carrier screening is available to the general population. That carrier rate is one in 30.
• Fanconi anemia, a DNA repair disorder that leads to a range of symptoms including thumb and arm abnormalities, skeletal abnormalities, kidney problems, skin discoloration, small head or eyes, mental retardation or learning disabilities, gastrointestinal difficulties, small reproductive organs in males and defects in tissues separating heart chambers. There are at least five genes implicated Fanconi anemia-and it only takes one of them going awry to cause the disease. Type C accounts for most cases of FA in the Ashkenazi Jewish population. Commercial testing is available for this mutation. The carrier rate among the Ashkenazi Jewish population is about one in 89.
• Niemann-Pick disease is a metabolic disorder caused by insufficient quantities of sphingomyelinase. The result is accumulation of the fatty substance sphingomyelin in the spleen, liver, lungs, bone marrow and, in some patients, the brain. Patients with Type A-predominantly individuals of Ashkenazi Jewish descent-rarely live beyond 18 months. Commercial carrier testing is available for Type A. The carrier rate among the Ashkenazi population is about one in 90.
• Mucolipidosis Type IV is a rare autosomal recessive disease with a carrier rate of 1 in 140 among Ashkenazi Jews. It is a progressive neurological disorder with symptoms beginning in the first year of life. Survival is rare, and the child has severe developmental delays. There is no treatment available.

Other Diseases in Ashkenazi Jews

• Torsion dystonia is a muscle-control disorder with an autosomal dominant inheritance pattern, but only a 30 percent penetrance, which means it takes only one defective gene to create the possibility of the disease, but only 30 percent of individuals who inherit the mutation will develop the disease. A genetic test can determine whether a person of Ashkenazi Jewish descent has the mutation that produces 90 percent of the cases in that population. Though the frequency of the gene is still uncertain, it occurs in no more than one in 2,000 Ashkenazi Jewish individuals.