Genetic Diseases That Affect Sephardic Jews
Sephardic and Mizrahi Disorders
Routine screening for Sephardic and Mizrahi Jews includes carrier screening for cystic fibrosis and spinal muscular atrophy as well as for hemoglobinopathies (such as beta thalassemia — see below). The following list includes a selection of some conditions that are more common in different Sephardic and Mizrahi populations. More specialized screening will be dependent on the individual’s country of origin and the availability of testing.
• Beta Thalassemia
Beta thalassemia falls into the category of hemoglobinopathies, or hemoglobin diseases. Red blood cells rely on the protein hemoglobin to transport oxygen from the lungs to the rest of the body. When genetic mutations disrupt the production of hemoglobin, red blood cells aren’t produced appropriately, leading to anemia. Sickle cell disease, alpha thalassemia, and beta thalassemia are all hemoglobinopathies. Globally, beta thalassemia is the most common inherited single gene disorder. This disorder covers a spectrum of anemias, ranging in severity from mild (intermedia) to severe (thalassemia major or Cooley’s anemia). Beta thalassemia is most frequently seen in humid climates with a high incidence of malaria, such as Africa, the Mediterranean, the Middle East and Asia. Carriers are thought to have some resistance to malaria. For Sephardic Jews, the carrier rate varies by country of origin, for instance, 1 in 30 for Greeks and Italians and 1 in 10 for Iranians.
• Familial Mediterranean Fever
Familial Mediterranean fever (FMF) is an episodic condition that affects 1 in 200 Sephardic Jews. About 1 in 3 to 1 in 7 are carriers. A mutation of the MEFV gene is the culprit, hindering the body’s ability to control inflammation when it occurs. A result of the condition is amyloidosis, or potentially dangerous buildup of protein in organs and tissues.
• G6PD Deficiency
G6PD deficiency is the most common known human enzyme deficiency, affecting 400 million people worldwide, most frequently in areas with a high incidence of malaria, such as Africa, the Mediterranean and Southeast Asia. About 65 percent of male Kurdish Jews have the disease. Carriers are thought to have some resistance to malaria. Because the genetic mutations are sex-linked, most cases occur in males. Females who carry one mutation are generally not affected because the normal copy of the gene on their second X chromosome compensates for the defect. Affected males can pass the mutation to a daughter, but it is unlikely that she would have symptoms, for this reason.
The disease is caused by insufficient glucose-6-phosphate dehydrogenase (G6PD), an enzyme found in red blood cells, causing the cells to break down faster than they can be replenished. This results in hemolytic anemia, which can vary in severity from lifelong anemia to rare bouts to no symptoms. Anemia in those who are G6PD deficient can also be induced by certain oxidative drugs, infections, severe stress or ingestion of fava beans. The most severe form of the disorder is called favism, after the legume.
• Glycogen Storage Disease, Type III
Glycogen storage disease type III (GSD III) is caused by an enzyme deficiency that prevents liver and/or muscle tissue from completely breaking down stored glycogen into glucose, which the body metabolizes. Glycogen is a carbohydrate that serves as one of the primary fuel reserves for the body’s energy needs. Stores of glycogen power the body during times of fasting and exercise. The progressive buildup of glycogen caused by the enzyme deficiency can cause muscle wasting and organ failure. In the Sephardic community, GSD III is primarily found among Jews of North African descent. About 1 in 5,400 North African Jews has this disease and 1 in 35 is a carrier.
Chana Wiesman, a genetic counselor at Montefiore Medical Center and The Program for Jewish Genetic Health of Yeshiva University and Albert Einstein College of Medicine, contributed to this list.