Jewish Genetic Conditions: Impacting Populations from Santa Fe to Samarkand

Jewish genetics today – whether Ashkenazi, Sephardic and Mizrahi – can be difficult. For generations, people have been marrying others who may not know their own genetic or ethnic background. Thus, it can be difficult to sort out.

The majority of Jewish genetic conditions are found among Ashkenazi or Eastern European origin Jews. Fewer are found among Sephardim, and still fewer among Mizrahi. It is strange as all Jewish communities practiced endogamy (within the family) for thousands of years. While Ashkenazi generally consciously avoided cousin marriage when they began migrating to the US and elsewhere in the late 1800s, among Sephardim and Mizrahim, it is still a preferred form of marriage.

Additionally, we know that many Sephardim migrated into Eastern Europe and married with the Ashkenazi community. Several studies and DNA projects have confirmed this. Thus, the whole idea of who is who is somewhat muddied. If your ancestors were Sephardim who moved to Belarus, perhaps that origin was passed down, perhaps it wasn’t. If you are asked, and know nothing about that Sephardic origin, you will say “Ashkenazi,” thus skewing the database.

Many readers will remember the tragedy of Tay Sachs disease before genetic testing became commonplace and nearly eradicated it. While the Ashkenazi Jewish carrier frequency is 1 in 27, the Sephardic-Mizrahi Jewish carrier frequency is 1 in 125. Because early advocates kept speaking about Ashkenazi couples testing for Tay Sachs, many Sephardim and Mizrahi couples felt they were safe – no one spoke about it – and they did not test, not realizing that it is also found in their own communities.

According to the Jewish Genetic Diseases Consortium (see side bar), there are some 10 conditions common to all Jewish groups, some 59 Ashkenazi conditions, and some 49 Sephardic/Mizrahi conditions.

According to SHORE, Sephardic and Mizrahi Jews can be defined as any Jews who are not of Ashkenazi origin. However, this group includes those with ancestors from Persia (Iran), Yemen, North Africa (e.g., Morocco, Tunisia), Spain, Italy, the Balkans, Iraq, India, etc. These distinct subgroups of Jews evolved in the Middle East, Mediterranean, South and Central Asia with some disorders unique to each subpopulation.

Hereditary Inclusion Body Myopathy (HIBM), a rare recessive genetic disease that causes late-onset muscle degeneration, has a Persian Jewish carrier rate of 1 in 15, more common than Tay Sachs in Ashkenazim. There is no cure or treatment. HIBM has been documented among non-Jews also, including Kurdish Iranians, Asian Indians, Caucasian Americans and Japanese. Before 2010, all tests for HIBM were sent to Hadassah Hospital in Israel where it was first identified by chance in 1979 in a patient thought to have muscular dystrophy.

Pseudocholinesterase Deficiency – anesthesia sensitivity resulting in paralysis of respiratory muscles – is quite frequent in the Persian and Iraqi Jewish communities; 10% of Iranian Jews are carriers. If the patient is known to have it, appropriate anesthetic agents can be selected to mitigate problems. In Israel, if a patient is recognized as being Persian, medical providers will ask and test the patient. For those who have it, undetected, waking up from anesthesia after surgery can take much longer than normal, with perhaps worse results.

In addition to the incidence of BRCA breast (and other) cancers in northern New Mexico among Hispanic women, who are descendants of converso-origin early settlers, and who carry the same mutation as that carried by Ashkenazi women, there are other conditions.

Many are rare, and in some cases, difficult to diagnose. Here are two also found in northern New Mexico:

Pemphigus is a group of rare skin disorders that causes blisters of the skin, mucous membranes (mouth and elsewhere). Quite rare (1-10 cases per 1 million people), it is higher in those of Mediterranean and Ashkenazi Jewish descent (16-32 cases per 1 million people). It is a type of autoimmune disorder.

Machado-Joseph Disease (Spinocerebellar Ataxia Type III) is rare, inherited and affects the central nervous system, characterized by slow degeneration of particular areas of the brain. Onset varies from early teens to late adulthood. The late-onset form appears at 70 or older, the patient stumbles or falls, has slurred speech and loss of muscle in arms and legs. It affects individuals of Portuguese descent, particularly from the Azores. It is suggested that the original mutation may have arisen among Sephardic Jews living in northeastern Portugal and then spread to the Azores, South America, etc. Many of those with MJD, in Portugal and the US, bear family names traditionally attributed to Sephardim.

The five most common Sephardic and Mizrahi Jewish conditions are based on country of origin in Jews of North African, Italian, Middle Eastern, Persian or Iraqi descent.

Here are some of the most common Sephardic genetic conditions.

Beta Thalassemia is a hemoglobin disease. Red blood cells with genetic mutations disrupt hemoglobin production which leads to anemias ranging from mild to severe (thalassemia major or Cooley’s anemia). is seen in humid climates that are humid with a high incidence of malaria, such as Africa, the Mediterranean, the Middle East and Asia.

The carrier rate varies according to country of origin, such as 1 in 30 for Mediterraneana (Italians, Greeks), 20% Kurdish Jews, 10% Iranians, 2-4% Middle Eastern and North African Jews. The disease frequency is about 1 in 3,600 individuals of Mediterranean and Middle Eastern descent. What is fascinating is that it is also found in people from several villages in Poland.

Familial Mediterranean Fever (FMF) is an episodic condition that affects 1 in 200 Sephardic Jews. Between 1/3 to 1/7 are carriers. The cause is a mutation of the MEFV gene, which stops the body’s ability to control inflammation. A result is amyloidoisis or a dangerous buildup of

protein in organs and tissues. It occurs most commonly in Jews of North Africa and Iraqi ethnicity and in those with Turkish heritage.

G6PD Deficiency is the most common human enzyme deficiency. It affects some 400 million people of all races worldwide, most frequently in places with high malaria rates, such as Africa, the Mediterranean and Southeast Asia. Carriers are thought to have some resistance to malaria. Sex-linked, most cases are in males. Females who carry one mutation are usually not affected. Males can pass it to a daughter. It is caused by not enough G6PD, an enzyme in red blood cells which causes cells to break down faster than they can be replaced, resulting in hemolytic anemia, varying from severe to no symptoms.

The anemia can be aggravated by certain drugs, infections, stress or eating fava beans (favism). The carrier rate is 50% Kurdish Jews, 25% Iraqi Jews. The disease frequency is about 60-70% male Kurdish Jews, 30% Sardinian males, 13% Saudi males, 11% Iranian males and 10-15% African-American males.

Glycogen Storage Disease, Type III is caused by an enzyme deficiency preventing liver and/or muscle tissue from breaking down stored glycogen into glucose, metabolized by the body. Glycogen, a carbohydrate, serves as a primary fuel reserve for energy needs.  But its buildup, caused by the enzyme deficiency, can cause muscle wasting and organ failure.  Among Sephardim, it is primarily found among Jews of North African descent. Carrier rate: 1 in 35 North African Jews. Disease frequency: About 1 in 5,400 North African Jews (rare).

Wolman Disease involves the breakdown and use of fats and cholesterol in the body. Harmful lipid amounts accumulate in the spleen, liver, bone marrow, small intestine, adrenal glands and lymph nodes. It is caused by LIPA, a lysosomal acid gene mutation that causes a shortage of lipase.

Learning about these genetic conditions helps us learn about ourselves and our families. Knowing, perhaps, that a family that comes from two small Polish villages carries a condition generally found only among Sephardic and Mediterranean Jews, helps us to understand the world of our ancestors and their wide migrations.


Sarnoff Center for Jewish Genetics (Chicago, Illinois)

Jewish Genetic Disease Consortium (JGDC)

SHORE For Life (Sephardic Health Organization for Referral and Education)


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