Handbook of Genetic Counseling/Coeliac Disease

Genetic etiology of the diseaseEdit

  • Celiac disease is an inherited condition where gluten proteins found in grains trigger an immune system attack on the lining of the small intestine. While celiac disease can be life threatening, many times it is not. It is a life altering disorder with symptoms such as diarrhea, fatigue, nausea and weight loss. Celiac is also linked to other autoimmune disorders and is now believed to lead to osteoporosis, anemia, infertility and cancer if left untreated.
  • Inheritance: the genetics of Celiac disease is simplest of the autoimmune diseases, with autosomal recessive inheritance and an environmental factor, gluten.
  • Risk factors: Family history (highest risk is in the non-affected identical twin of a celiac), genetic predisposition (DQ2,DQ8), pre-existing intestinal injury, degree of environmental exposure to gluten (how frequent and how much gluten), immune status and lifestyle triggers (stress, trauma, surgery, puberty).
  • Treatment: A lifelong Gluten-Free diet is the only treatment; careful avoidance of all grains will ameliorate many related symptoms.

Incidence, genetic frequency and riskEdit

Studies show an incidence of 1:133 people in the United States – common in 1:120 Worldwide - qualifies Celiac Disease as a global epidemic. The disease is inherited in 95-99% of people with Celiac disease testing positive for at least one of two DQ specific serotype patterns and some may have two copies of one or test positive for both DQ2 and DQ8. Professional medical experience with gluten intolerance and celiac disease has shown the gluten sensitivity problem is more complex and extends beyond the defined risk celiac genes DQ2 and DQ8. Testing positive for two DQ specific serotype patterns; DQ2/DQ2, DQ2/DQ8, or DQ8/DQ8 carry much higher risk for celiac disease and significantly more severe forms of gluten sensitivity.

  • Type DQ2: low risk for celiac disease and gluten sensitivity is found in greater than 90% of Northern European celiac disease patients occurs in 12 - 26% of controls.
  • Type DQ8: low risk for celiac disease and gluten sensitivity
  • Type DQ2/DQ2: higher risk for celiac disease and more severe gluten sensitivity
  • Type DQ2/DQ8: higher risk for celiac disease and more severe gluten sensitivity
  • Type DQ8/DQ8: higher risk for celiac disease and more severe gluten sensitivity
  • Type DQ4/DQ4: No significant risks

A genetic test report stating DQ2 negative AND DQ8 negative reinforces a medical diagnosis that you do not carry the celiac disease gene. Unfortunately, a negative Celiac Disease report can be construed to mean that gluten is not a source of your problems. WRONG! All it teaches is that you probably do not have flattened villi! You still can have gluten intolerance with severe symptoms and risk of organ damage.

There are documented medical cases of celiac disease and the skin equivalent of celiac disease, dermatitis herpetiformis (DH) in individuals who have tested DQ2 and DQ8 negative. A prognosis that if you are DQ2 and DQ8 negative you are unlikely to have celiac disease or risk ever developing it, cannot be made with 100% certainty.

Clinical SynopsisEdit

Recognizing celiac disease on the basis of the various manifestations of the disorder is difficult. The strict definition of celiac disease - specific damage to the small intestine which can be identified as flattened villi - is linked with genes DQ2 and DQ8. It is possible to have a severe case of malabsorption combined with other symptoms with gluten sensitivity and still not have celiac disease.

  • GI:

Gluten intolerance Recurrent diarrhea

  • Heme:


  • Lab:

Antigliadin antibody

  • Inheritance :

Autosomal recessive vs. multifactorial

Age of onset, disease history, and life spanEdit

Celiac cases present as one of three types that can occur at any age.

  • Classic case: chronic diarrhea, weight loss, abdominal distension, anemia
  • Symptomatic case: Western Hemisphere experience is that symtomatic Celiacs average 11 years until diagnosis.
  • Asymptomatic case: atypical clinical manifestations of celiac disease, include osteoporosis, chronic fatigue, irritable bowel, and miscarriage

There is no test yet which is definitively diagnostic of celiac disease. Relief of symptoms or reversion of an abnormal intestinal biopsy to normal on a gluten-free diet is the most convincing evidence that an individual has celiac disease or gluten sensitivity.


  • Serum Blood tests: elevation of tissue transglutaminase (tTG), an enzyme (tTG > 000 mg/dl)
  • Gastro examination and biopsy for villi flattening in the stomach
  • Gluten challenge tests/gliadin assays
  • Genetic Molecular analysis of HLA genes (DQ)

Surveillance, management, and treatment optionsEdit

The general understanding among celiac disease patients is that once diagnosed, a series of problems may be over, but many others will begin. Particularly frustrating is the limited information regarding what constitutes a gluten-free diet, what is safe and what is not, how to check for compliance, the potential complications of untreated celiac disease or of a delayed diagnosis, and how often it is necessary to follow up with the gastroenterologist.

  • Children: The onset of illness in children most commonly occurs around age two, after wheat has been introduced into the diet. Concordance for celiac sprue in identical twins approximates 70% as compared with 30% concordance in HLA-identical sibs. The generally accepted practice is NOT to begin treatment of a gluten-free diet in children who have the genes for celiac disease but not yet tested positive for the enzyme tTG. Follow up testing in Children usually every 2 yr to monitor immune status. If a gluten-free lifestyle is the family norm, children should receive at least one slice of bread daily to provide valid testing results.
  • Teens: Teenagers may hit puberty late and be short in stature.
  • Adults: The onset of illness most commonly occurs in early adult life (third and fourth decades), but can occur at any time.

Antibodies which are specific for celiac disease, genetic screening of families of celiacs and testing select populations have identified asymptomatic individuals who have circulating antibodies and changes on intestinal biopsies characteristic of celiac disease. These individuals clearly have a gluten sensitivity but it is unclear whether they will develop the clinical features of celiac disease over time. Removal of wheat (gluten) from the diet of individuals with celiac disease or gluten sensitivity results in regeneration of the intestinal mucosal absorptive surface area and resolution of symptoms in most patients.

Differential diagnosesEdit

  • Failure to thrive
  • Short stature
  • Down syndrome
  • First degree relatives of patients with celiac disease
  • Chronic fatigue
  • Carbohydrate intolerance
  • Pancreatic deficiency
  • Diabetes Mellitus (Type I)
  • Dyspepsia
  • Esophageal reflux
  • Diarrhea
  • Constipation
  • Abdominal Pain
  • Reduced Bone Density
  • Osteopenia
  • Osteoporosis
  • chelitis
  • Hypocalcemia
  • Secondary hyperparathyroidism
  • Ataxia
  • Peripheral neuropathy,
  • Epilepsy (with and without occipital calcifications)
  • Iron Anemia
  • Folate Anemia
  • Vitamin B12 deficiency
  • Angular cheilitis
  • Recurrent aphthous ulcers
  • Dermatitis herpetiformis
  • Apthous stomatitis
  • Dental enamel defects
  • Delayed menarche
  • Premature menopause
  • Infertility
  • Spontaneous abortion
  • Primary biliary cirrhosis
  • Autoimmune hepatitis
  • Elevated transaminases
  • Sjogren's syndrome