In my epidemiology class, we did a unit on genetic disorders and disease screening. Genetic disorders are “rare”– at least until they happen to you.

Many of us are carrying a gene right now for some type of genetic disorder. But it’s only if the conditions are just right that a baby has a disorder or becomes a carrier.

Why?

Sometimes it has do with culture and geography. Communities that have been isolated either by culture or geography tend to have a smaller “pool” of marriage partners. So if one or two families in a small community are carriers, the gene can spread through the community over the years. In some communities where marriage between cousins was more common, genes for disorders became much more prevalent. Even things like conflict and war can contribute to genetic disorders. For example, some geneticists have suggested that the pogroms in Eastern Europe decreased the number of potential marriage partners within the Ashkenazi Jewish community, causing a further proliferation of certain genes.

Sometimes a particular gene actually gives carriers a survival benefit, like the way sickle cell trait protects against certain types of malaria.

And others, we just don’t know. Some disorders are uniformly distributed across racial and ethnic groups. They don’t seem to have any biological reason for being. They just are. And we are left to speculate on the existentialist reasons.

How rare is “rare”?

Dna With Unique ConnectionWell, it all depends on your genetics. 

Common Rare Genetic Diseases

Thalassaemia and Sickle cell disease

Both thalassaemia and sickle cell disease are hemoglobin disorders. Thalassemia causes blood cells to develop abnormally and affects people differently depending on how many mutated genes they have inherited and whether it’s alpha or beta thalassemia. Sickle cell disease causes the normally round red blood cells to be sickle shaped. This means the blood cells don’t fit through blood vessels properly and can cause periods of extreme pain and illness. Carriers can also have some health problems, which could account for the high rates of maternal and infant mortality and morbidity among African American women and infants. Thalassemia and sickle cell disease affect populations parts of the world where malaria is endemic (Sub-Saharan Africa, South America, Cuba, Central America, Saudi Arabia, India, and Mediterranean countries such as Turkey, Greece, and Italy). If your ancestors came from these parts of the world, you could be a carrier for one of these diseases. About 1 in every 500 African-American births and 1 in every 1000 to 1400 Hispanic-American births are affected with sickle cell disease. 1 in 12 African Americans are sickle cell trait carriers.

Haemophilia

Hemophilia is a bleeding disorder where the body lacks most or all clotting factor. Occurs evenly across different racial and ethnic groups. There are different types of hemophilia, all with varying levels of rarity. Hemophilia A occurs in about one in every 4,000 to 5,000 males worldwide, hemophilia B is estimated to be in 1 in every 20,000 men and hemophilia C is estimated to occur in about one case per 100,000 people in the U.S. This disease is famous for contributing to the end of the Russian Romanov dynasty.

Cystic Fibrosis

Cystic fibrosis causes the lungs to produce too much mucus. It affects most racial and ethnic groups, but Caucasians have the highest risk. The overall risk in White newborns in 1 in 2,500 to 1 in 3,500. The risk is much lower in other ethnic groups. In the United States, the risk for African American babies is about 1 in 17,000 babies.  For Asian American babies the risk is about 1 in 31,000. This disorder is going to hit the mainstream with the new movie Five Feet Apart.

Tay Sachs disease

Tay Sachs disease is a fatal genetic disease in which harmful quantities of a fatty substance called Ganglioside GM2 accumulate in the nerve cells in the brain. This causes nervous system degradation and eventually death. Tay Sachs disease affects Ashkenazi (Eastern European descent) Jews at a very high rate. In the United States, 1 in 27 Jews is a carrier for Tay Sachs. Other ethnic groups have a high risk as well. French Canadians from the St. Lawrence River area and Cajuns from Louisiana also have a 1 in 27 prevalence of Tay Sachs carriers. Irish Americans have a higher than average risk at 1 in 50 individuals being carriers. The risk for non-Jews and for Sephardic (Middle Eastern) Jews is 1 in 250.

Fragile X syndrome

Fragile X syndrome is caused by a “fragile” site at the end of the long arm of the X-chromosome. This fragile site is the result of a premutation which can be passed as a premutation or a full mutation to a child. Fragile X is an X-linked disorder, which means that it is only inherited on an X chromosome, so a father can pass the premutation to his daughters but not a son and mother can pass the premutation and mutation to both sons  and daughters. This makes the inheritance a little more complicated than a simple “two recessive genes”. Fragile X causes varying levels of developmental delays and it tends to affect boys more strongly than girls.

Fragile X Syndrome is distributed pretty evenly across all ethnic groups with an average of 1 in every 2000 males and 1 in every 4000 females of all races and ethnic groups. Worldwide, 1 in 3600 males and 1 in 4000 to 6000 females have some form of Fragile X syndrome. 1 in 259 women of all races carry the Fragile X premutation. The number of men who are carriers is thought to be 1 in 800 of all races and ethnicity. Carrier females have a 30% to 40% chance of giving birth to an affected male child and a 15 to 20% chance of having an affected female child.

Huntington’s disease

Huntington’s disease is a degenerative brain disorder, in which affected individuals lose their ability to walk, talk, and reason. This disease begins between ages 30-45, and every individual with the gene for the disease will eventually develop it. Huntington’s is an autosomal dominant genetic disorder which means that if one parent carriers the defective Huntington’s gene, his/her offspring have a 50/50 chance of inheriting the disease. Huntington’s disease occurs pretty regularly across all ethnic and racial groups.In Western countries, it’s estimated that about five to seven people per 100,000 are affected by HD. Woody Guthrie, the songwriter who wrote “This Land Is Your Land” had Huntington Disease. 

Muscular dystrophy

Muscular dystrophy is a group of genetic diseases that cause progressive muscle weakness and wasting. Duchenne and Becker muscular dystrophy are among the most common with Duchenne being the most common. Duchenne affects all races, but there is a much higher rate among among Hispanics and Whites. The estimated incidence of Duchenne and Becker muscular dystrophy is 1 in every 7,250 males aged 5 – 24 years.

And then there are some rare genetic diseases…

Congenital adrenal hyperplasia

CAH is a disorder of the adrenal and sex hormones. Some types are fatal and others are not. CAH has a worldwide incidence of 1 in 13,000 to 1 in 15,000. In the United States CAH incidence is 1 in 10,000 to 1 in 23,000 depending on the ethnic make up of a population. Ethnicities that are at risk for CAH are Hispanics, Italians, Ashkenazi Jews, Croatian/Slavic, Iranians and Yupik Inuits. (Among Yupik Inuits, the incidence of CAH is 1 in 300 births.)

Maple syrup urine disease

Maple syrup urine disease is a disorder in which the body can’t properly process some amino acids. This causes poor feeding, vomiting, developmental delays, lethargy and the sweet smelling urine which gives the disease it’s name. Maple syrup urine disease occurs in 1 in 185,000 infants worldwide. But it is especially common among Old Order Mennonite communities where the incidence is 1 in 380 births.

Treacher Collins Syndrome

TCS affects the development of the face, ears, eyes and teeth. Most individuals have normal intelligence, but may have some hearing or sight impairments or respiratory issues. The facial features are distinctive and sometimes ears or teeth are absent. TCS occurs in about 1 in 50,000 births and affects boys girls and all ethnicities equally. The boy in the book and movie Wonder had Treacher Collins Syndrome.

Krabbe disease

This is a fatal degenerative neurological disorder that has controversially been added to the newborn screen in three states (New York, Missouri, Ohio). Most cases are found in people with Northern European heritage and a couple of isolated Muslim communities in Israel. The estimated incidence of Krabbe disease has been placed at 1 in 100,000. However, the newborn screen for Krabbe disease in New York and Missouri showed the incidence to be lower than anticipated in that area at 1 in 500,000 births.

And then there are really rare genetic diseases…

Fumarase deficiency

This extraordinarily rare disease had only 13 cases in the whole world…until 20 cropped up in the small polygamist community of the Fundamentalist Church of Jesus Christ of Latter Day Saints (FLDS) on the Utah-Arizona border. The cause was inbreeding, which led to a media sensation and a great deal of attention from the medical community. Though the news media predicted the end of the cult because of the high number of birth defects cropping up in their community, there will probably be fewer infants in general since leader Warren Jeffs outlawed sex for his followers in 2011.

One interesting thing to note is that our world has gotten so much bigger in the 250 years. People no longer have as few choices in marriage partners as they did when you never left the village you grew up in. Emigration to the New World brought about a more diverse gene pool. International air travel has made it easier for people to visit and move to new countries. Civil conflict has brought new people into different countries. Social barriers have dissolved and it’s more acceptable to marry someone from a different race or culture. All of these changes could mean that we see less of some of these diseases in the future as we become a more connected world.

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