Lack of One Enzyme Triggers Illness

Gaucher Disease is a rare, inherited disease caused by a hereditary deficiency of a single essential enzyme, glucocerebrosidase, according to the National Gaucher Foundation (NGF).

Because this enzyme is necessary for breaking down aging blood cells, its lack causes some cells to become engorged. This condition eventually crowds the liver, spleen, bone marrow and lung cells and causes those organs to swell, disrupting production of blood cells in bone marrow and causing destruction of bones.

Genetic counselor Amy White of the Lysosomal Diseases Treatment Center in the Genetic Center at Children’s Hospital of Wisconsin put it this way: “Lysosomes are like the garbage disposals of our cells. Their job is to collect and get rid of the waste products.”

Symptoms of Gaucher Disease can occur in childhood or adolescence, but the disease is most often diagnosed in adults, according to the Center for Jewish Genetic Diseases Web site.

An enlarged spleen and liver are often the first noticeable symptoms in children, said White, a member of the National Society of Genetic Counselors.

“And these are pretty noticeable,” she added. “You see a skinny kid with a big belly.”

The most common symptoms in adults are bone breaks, bone infection, unusual bleeding and tiredness, White said. An “easy and accurate blood test” can diagnose Gaucher Disease and identify carriers.

The effects of the symptoms vary, depending on the severity of the disease, but they can be managed with biweekly infusions of Cerezyme, an enzyme manufactured from Chinese hamster ovaries, which are referred to as “cho.”

“It uses recombinant [artificially created] DNA technology that is five to seven years old. It is the oldest enzyme therapy around, so we know the most about it,” White said.

Gaucher Disease is one of three lysosomal diseases treated at the center, and is the only one that primarily affects Jews. The other two, Fabry Disease and MPS 1, also called Hurler’s Disease, strike across ethnic lines.

The prevalence of Gaucher Disease in Ashkenazi Jews occurs because of something geneticists call the “founder effect.” This refers to a genetic trait or disease that has a high frequency in a contemporary population, because the gene was introduced by a founder into a small, often geographically or socially isolated group of people whose numbers then rapidly expand, according to a medical paper distributed by the NGF.

Ashkenazi Jews became susceptible to a variety of hereditary diseases because of their long history of “sudden periods of population contraction — the Crusades, pogroms, the Holocaust — followed by concentration in restricted areas — ghettos, the Pale of Settlement — and then temporary multiplication to large numbers.”

Though Tay-Sachs Disease, which affects one in about 2,500 Ashkenazi Jews, is the most well known of about 10 genetic diseases afflicting that population, Gaucher Disease is much more widespread. One in an estimated 450 Ashkenazi Jews suffers from the disease, and one in 14 is a carrier, according to the NGF.