Celiac Disease: All In The Family

Aliases: celiac disease, coeliac disease, celiac sprue, non-tropical sprue, and gluten sensitive enteropathy

Being gluten free is in fashion, but while it’s optional for some, it’s obligatory for the many suffering from celiac disease (CD). CD is an autoimmune disorder that’s estimated to affect 1 out of every 100 people2. The actual count is unknown, because a staggering 85-90% of people with the condition are undiagnosed1. That means that in the US alone, 2.5 million people with CD are unaware that they have the disease2.

Although public awareness of CD has certainly increased recently (to the point where people are sick of hearing the phrase “gluten free”), improvement in diagnosis alone doesn’t explain the huge jump in case numbers. In fact, it doesn’t come close. Even controlling for better detection, the number of people with CD is growing rapidly; prevalence rates are doubling every 20 years. Environmental factors, like greater wheat consumption, are thought to have played a role in this astronomical leap in prevalence, but the importance and extent of their contribution remains unclear1.

While the environmental triggers and even the symptoms of this complex disease are difficult to disentangle (see below), its genetics have proved relatively straightforward. CD is the most common genetically-based food intolerance in the world, and it hinges on two genes. People with the HLA-DQ2 or DQ8 genes are at a greater risk for CD, these genes contribute about 40% of the disease risk. Its strong genetic links keep CD in the family; having an immediate family member with the disease gives you a 1 out of 10 chance of having it1.

celiac disease
Gluten free is the way to be.

Cause: Like most autoimmune diseases, CD results from a combination of genetic predisposition and environmental factors. Once the disease is active, it is expressed when the ill consume gluten, a protein found in several grains, including wheat, rye, and barley2. Several environmental factors increase the likelihood of developing CD, including early infections, infant gut microbiota, and the amount and timing of the first exposure to gluten1.

Consequence: When gluten is digested by someone with CD, their body misidentifies it as a pathogen and sets off an immune response that attacks the lining of the small intestine, damaging the villi. This causes inflammation and impairs nutrient absorption, which can lead to an array of about 300 possible symptoms, including abdominal bloating and pain, weight loss, fatigue, migraines, irritability, and depression2. Although it is a disease of the gut, gastrointestinal symptoms can be minor or even absent, while symptoms outside the digestive tract can be major1. And to heap injury upon injury, CD is also associated with a range of other conditions, including anemia, osteoporosis, infertility, epilepsy, Type I diabetes, multiple sclerosis, and intestinal cancers2. The older a person is when he or she is diagnosed, the greater his or her chance of developing another autoimmune disorder; one study found that people diagnosed with CD after age 20 had a 34% chance of developing another autoimmune disorder2.

Cure: Because of its ridiculous number of symptoms, definitively diagnosing CD is a tricky business. Typically, once the disease is suspected a blood test is used to look for celiac-specific antibodies and, if positive, damage to the intestinal lining is then assessed with a biopsy. The only treatment for celiac disease is avoidance: a strict gluten free diet1. Some ties bind for life.

References

  1. Guandalini, S. & A. Assiri. 2014. Celiac disease: a review. JAMA Pediatrics, 168: 272-278.
  1. What is Celiac Disease? Celiac Disease Foundation. Web. 9 June 2015.

Image source: Creative Commons, http://www.marksdailyapple.com/gluten-free-fad/#axzz3d6qrTOfc

Hereditary Deafness: Family Ties

Aliases: hereditary deafness

While deafness is not a disease (it’s a medical condition), hereditary deafness offers an excellent example of genetic inheritance, making it an ideal topic for this June’s theme, family. There is an obvious connection between an inherited condition and kinship. After all, you share your genes with your relatives. However, there are also more subtle ties between the two. Inheritance can happen in a number of different ways (see the Cause section below), and the pattern of inheritance can have a profound effect on the way a condition is treated by family members and the society at large.

There are many populations that have high levels of hereditary deafness. They usually occur in geographically or culturally isolated communities, where the gene flow (movement of genes) is limited3. The most iconic example may be Martha’s Vineyard. Hereditary deafness reached Martha’s Vineyard in the 17th century during colonization and radiated through the population until 1 out of every 155 (0.7%) islanders were born Deaf, nearly 20 times the US national rate2. This increase reached its peak in the town of Chilmark, where the 1 out of every 4 people were born Deaf1.

A recessive gene was the most likely cause of the hereditary deafness on Martha’s Vineyard. Unlike dominant traits, which only require one copy of the gene, and are passed down directly in families, recessive traits require two copies, one from each parent. The recessive pattern of inheritance is indirect, diffusing the trait across the family tree, making Deaf people less likely to have Deaf immediate family members (although likely to have Deaf people in their extended family). Because nuclear families often included both Deaf and hearing people, Martha’s Vineyard became a bilingual society, with most islanders communicating comfortably in both English and sign language2.

hereditary deafness
Sometimes it needs to be said.

This social integration led to 3 times as many marriages between Deaf and hearing people on Martha’s Vineyard than off the island2. In turn, these families contributed to 250 years of assimilation4, creating a “shared signing community”1 that outlasted hereditary deafness on the island. The high concentration of deafness quickly dissipated in the twentieth century4, when better transportation and communication with the mainland caused a higher rate of immigration to the island, and the last hereditary Deaf person on Martha’s Vineyard died in the 1950s4. But despite the lack of necessity, sign language continued to be used well into the 1980s1. I guess some ties bind.

Cause: Hereditary deafness can be conductive (caused by abnormalities of the external ear or the ossicles of the middle ear), sensorineural (caused by a malfunction of inner ear structure), or a combination. Deafness can be passed down by several types of inheritance: it can be autosomal recessive (requiring the same gene from both mother and father to result in deafness) autosomal dominant (only requiring one copy of the gene, passed directly through generations), X-linked recessive (carried on the X chromosome) or mitochondrial (from a gene in the mitochondria, only passed through the mother). Non-syndromic deafness (has no associated medical disorders) is usually caused by a mutation in one gene and has fairly high heritability (likelihood of being inherited), depending on the type of inheritance (dominant: 75-80%, recessive: 20-25%, X-linked: 1-1.5%)5. By 2001, 11 genes had been identified for autosomal dominant non-syndromic deafness alone6, and more than 400 genetic syndromes are associated with hearing loss5.

Consequence: While hereditary deafness can be syndromic (associated with malformations of the ear or other medical disorders), 80% of genetic deafness is non-syndromic6. Hearing loss may be pre-lingual (before speech develops) or post-lingual5.

Cure: Hereditary deafness is identified with both physical and genetic testing. Because deafness is not considered a disease, a “cure” is not the appropriate way to discuss the treatment of the Deaf. There are many management options for deafness, ranging from hearing aids to cochlear implants5.

References

1. Kusters, A. Deaf utopias? Reviewing the sociocultural literature on the world’s “Martha’s Vineyard situations”. Journal of Deaf Studies and Deaf Education, 15(1):3-16.

2. Lane, HL, R Pillard, & M French. Origins of the American Deaf-world: assimilating and differentiating societies and their relation to genetic patterning. Sign Language Studies, 1(1):17-44.

3. Marscheck, M & PE Spencer, eds. Oxford Handbook of Deaf Studies, Language, and Education. New York: Oxford University Press, 2003. Print.

4. Novakovic, J. Hereditary deafness on Martha’s Vineyard collection. Martha’s Vineyard Museum. Web. 15 June 2014. http://www.marthasvineyardhistory.org/collections/fa_pdfs/RU%20310–Hereditary%20Deafness.pdf

5. Smith, RJH, AE Shearer, MS Hildebrand, & G Van Camp. Deafness and hereditary hearing loss overview. Gene Reviews. 9 January 2014. Web. 15 June 2014. http://www.ncbi.nlm.nih.gov/books/NBK1434/

6. Zhao, HB. Congenital deafness. American Hearing Research Foundation. March 2007. Web. 4 June 2014. http://american-hearing.org/disorders/congenital-deafness/

Image source: Creative Commons, http://www.alldeaf.com/general-chat/75553-tattoo.html