Genetic screening for coeliac disease – Dr Kunal Thacker

Paediatric Gastroenterologist Dr Kunal Thacker will be presenting at the Coeliac Awareness Week information session at the North Shore Private Hospital on Wednesday, 18 March 2020.  

Dr Thacker has written the following article to help readers better understand how genetic testing relates to coeliac disease and the diagnostic process.

Coeliac disease (CD) is an immune disorder triggered by dietary gluten in people who carry HLA DQ2 and/or HLA DQ8 genes. These genes predispose carriers to developing an abnormal immune response to eating gluten that causes damage to the small bowel (intestine) along with varying degrees of a wide range of symptoms and associated conditions.

The risk of CD in family members of someone with CD is 10%. Because of this link, it is recommended that these family members are screened for CD. HLA testing may be helpful in this situation (Refer to the Family Screening letter available for download from In infants and young children, genetic testing does not always require a needle (a buccal/cheek swab can be taken). 

But genetic screening has limitations. Approximately 50% of the general population in Australia carry at least one of these genes. Of the general public who have no other risk factors for CD and who carry the gene, only 3% develop CD over their lifetime. Thus, for most people who carry the gene the risk of developing coeliac disease is very low. 

The HLA DQ2 gene is identified in 90-95% of those who are diagnosed with CD and the rest carry HLA DQ8 gene. It is very rare (<1%) that these genes are not identified in those diagnosed with CD. Hence, absence of these genes has a good negative predictive value, i.e. effectively rules out CD as an underlying diagnosis. 

Genetic screening does not in itself diagnose CD, but can be useful in the following situations:

  • When coeliac serology and/or small bowel examination is inconclusive or unclear
  • When there has been failure to improve on a gluten free diet
  • When a person has commenced a gluten free diet prior to assessment by serology or small bowel examination and are unwilling or unable to undertake an oral gluten challenge prior to investigation
  • In patients clinically assessed to be at higher-risk of coeliac disease, in order to exclude those where further testing for coeliac disease is not required.

You may find the additional information about diagnosis on web page helpful, particularly the fact sheet available for download – Testing and diagnosis of coeliac disease in children.

Members of Coeliac Australia’s MAC have developed an evidence-based approach to guide clinically appropriate use of HLA typing (genetic screening)

Dr Kunal Thacker works as a paediatric gastroenterologist and hepatologist at The Children’s Hospital at Westmead (CHW), Sydney. At CHW he is involved in regular educational and research activities with a focus on Inflammatory Bowel Disease and Eosinophilic Oesophagitis.

Irritable Bowel Syndrome and Low FODMAP diet

Irritable Bowel Syndrome (IBS) is a common gastrointestinal (GI) condition wherein the exact cause remains unknown. It is characterized by recurrent abdominal pain, bloating, distension, cramping, flatulence, diarrhoea and/or constipation. It has been proposed that in those with IBS, the nerves that affect perception of intestinal stretching and motility, may have some disturbances secondary to interaction between factors such as genetics, psychosocial and post-inflammatory changes after GI infection. Diagnosis of IBS can be difficult as there is no structural, biochemical or physiological abnormality demonstrated in those with IBS. Thus, IBS diagnosis is based on symptoms reported.


Pharmacological treatment for IBS is tailored and dynamic as symptoms vary in the same individual over a period of time as well as between individuals.


The low FODMAPs diet is one dietary strategy that has been used to manage IBS symptoms. This is considered to be a second line dietary approach after the dietary and lifestyle factors are assessed and managed, as these may contribute to IBS symptoms too. Current evidence suggests that low FODMAP dietary approach (compared to no dietary intervention) can reduce GI symptoms in up to 75% of individuals with IBS. FODMAPs are types of sugar (short-chain carbohydrates) naturally found in foods, which are poorly absorbed in some people or not absorbed at all. FODMAP is an acronym for these sugar molecules and it stands for Fermentable Oligosachharides Disachharide Monosachharide And Polyols.


One can malabsorb either one or a combination of FODMAPs in their small bowel, which then end up in large bowel in undigested forms. This leads to:
a) Increased delivery of water into the large bowel to dilute the concentrated
undigested FODMAPs (as they are osmotically active)
b) Increased gas production secondary to large bowel bacteria feeding on them
c) In turn, bowels expand and their motility is affected (i.e. functioning of bowel
muscles is altered)


In individuals susceptible to IBS, these events could have a combined effect of bowel distension and altered bowel motility causing people to report symptoms like bloating, flatulence, abdominal pain and altered bowel habits (constipation and/or diarrhoea). The low FODMAP dietary approach assists in identifying the potential FODMAP of concern for the individual. Accordingly, a planned and systematic reintroduction challenge of high FODMAP foods will identify which foods can be reintroduced to the diet based on individual’s tolerance levels to achieve symptom relief. It is very important that this is done in consultation with an Accredited Practising Dietitian (APD) to ensure nutritional adequacy throughout the trial and reintroduction phase of low FODMAPs diet.


The implementation of dietary approach can take between 12-14 weeks. It is important to note that long-term restriction of FODMAPs is not recommended as that could lead to nutritional deficiency and may have an unfavourable effect on GI microbiota.

Eosinophilic Oesophagitis in children

Eosinophilic Oesophagitis (EoE) is a relatively new disease causing significant upper gastrointestinal morbidity in children. The diagnosis is based on symptoms of oesophageal dysfunction in association with presence of at least 15-eosinophil/high power field in oesophageal biopsy specimen and exclusion of other causes of oesophageal eosinophilia.


Incidence of EoE is approximately 1 new case per 10,000 per year and this is thought to be an underestimate. There has been a steady rise in the incidence over the last decade. A seventeen-fold rise in prevalence of biopsy proven EoE over a decade was demonstrated for children of Western Australia in 2006. This parallels with rise in allergies.


Children present with variable symptoms compared to adults where dysphagia is a universal presentation. Constellation of symptoms is age dependent. Younger children experience vomiting, regurgitation, water brash and decreased appetite. Infants and toddlers are more likely to present with difficulty feeding, manifest as gagging, choking, refusal of certain foods (mainly solids) and vomiting. Dysphagia and food bolus impaction is not commonly seen until adolescence. Children with EoE are usually slow eaters, avoid certain meats, cut meat in small pieces and consume a lot of water with their meals. There is higher rate of atopy (asthma, eczema, hay fever and allergies) in children with EoE when compared to children without EoE. Children with some other medical disorders are known to have increased risk to develop EoE such as tracheoesophageal fistula, Down syndrome, heart defects and connective tissue disorders.


Symptoms of EoE overlap with Gastroesophageal reflux disease (GERD). There can be significant delay in diagnosis, a study in adults documented delay of up to 6 years from onset of symptoms and this is more in children. Risk of complications (oesophageal stricture) increases with duration of untreated disease. Gastroscopy and biopsies remains the only test to confirm the diagnosis. Macroscopic appearance in younger children show inflammatory changes (loss of vascularity, linear furrowing and white exudate), where as older children and adolescents may demonstrate additional fibrotic features (Trachealization, crepe-paper oesophagus and strictures). There are a proportion of children who may have macroscopically normal oesophageal mucosa and diagnosis is made on histology.


Topical corticosteroids and dietary elimination is the mainstay of treatment for children with EoE. Six-food elimination diet has been superior to skin prick directed elimination diets in children and adults. New pharmacological modalities including biologic therapy are being explored as a result of improved understanding of pathophysiology.


Eosinophilic Oesophagitis has emerged as an important clinical entity due to rise in incidence and high index of suspicion helps with early diagnosis. Gastroscopy in required to confirm the diagnosis. Treatment is required to prevent


complications. Insight in the natural history and long-term outcome is emerging. Future research is being directed to better understand pathophysiology, assess efficiency of non-invasive diagnostic test and individualized approach to treatment.

Diagnosis of Coeliac Disease In Children – To Scope or Not To Scope?


Coeliac disease (CD) is an immune-mediated systemic disorder elicited by gluten and related prolamines in genetically susceptible individuals. It is characterised by the presence of a variable combination of gluten dependent clinical manifestations, CD specific antibodies, HLA-DQ2 or HLA- DQ8 haplotypes and enteropathy.


Coeliac Disease is now considered to be one of the commonest multi-organ disorders in genetically predisposed individuals and to reduce the burden of disease. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) proposed new consensus guidelines based on available evidence in 2012 for non-invasive diagnosis of CD. As over the years, the diagnostic accuracy of the serology based testing has improved significantly with more than 95% specificity of Anti Endomysial antibody IgA (Anti EMA) and Anti Tissue Transglutaminase antibody (Anti TTG) IgA. Conventionally anti-TTG has been the best screening blood test due to its high sensitivity and specificity, simpler technique and less expensive. Genetic screening has been reserved to rule out the presence of CD in suspicious cases rather than assist the diagnosis of CD.

Guideline classifies children in 2 broad categories of symptomatic and asymptomatic. It proposes not to do a biopsy for symptomatic children who carry the gene HLA DQ2/HLA DQ8 with highly positive anti TTG (>10 times) and positive EMA as shown below.


Children with either chronic diarrhoea, failure to thrive, weight loss, stunted growth, delayed puberty, amenorrhoea, iron-deficiency anaemia, nausea, vomiting, chronic abdominal pain, cramping or distention, chronic constipation, chronic fatigue, recurrent mouth ulcers, dermatitis herpetiformis like rash, pathological fracture and abnormal liver biochemistry would be included in this group. Thus, children without overt symptoms and with symptoms but not fulfilling the above criteria are recommended to have an endoscopy and biopsy.


These guidelines are being assessed in prospective studies throughout the world and may provide more insight into its application shortly. Although there are no studies from Australia its widespread application has been questioned in some retrospective studies from North America and Europe. There are some limitations in our local setting as EMA antibody has high inter-observer variability and not easily accessible in Perth Metropolitan. Long term data on the outcome of children that are diagnosed without biopsy and histology is still not available. Hence, the current recommendation for all children would be to do a duodenal biopsy for confirmation of coeliac disease until we could have more prospective data for non-invasive diagnosis using the ESPGHAN guidelines. And those patients who are keen not to have an invasive procedure be made aware of these limitations.



  1.  Diagnosis of celiac disease: where are we heading after the ESPGHAN 2012 guidelines? J Pediatr Gastroenterol Nutr. 2014 Jul;59 Suppl 1:S13-5.
  2.  European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr. 2012 Jan;54(1):136-60.


Author competing interests- no relevant disclosures. Questions? Contact the author on 9340 8355


Diagnosis of Helicobacter Pylori in children – An Update


Infection with Helicobacter pylori (H. Pylori) is acquired in early childhood. The prevalence is higher in developing countries compared to developed countries including Australia. Complications are fewer in children with less than 10% of hose infected develop peptic ulcer disease (PUD) confirmed by endoscopy. A recent meta-analysis concluded that H. pylori infection in the absence of PUD is not associated with abdominal pain in children. Also as per European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) and North American Society for Paediatric Gastroenterology Hepatology and Nutrition (NASPGHAN), “test and treat policy” is not recommended for children with abdominal symptoms. There is no clear evidence to prove causality of other extra-gastric symptoms including otitis media, upper respiratory infections, dental diseases,food allergies, sudden infant death syndrome and short stature. H.pylori has been considered to be a significant risk factor for certain types of gastric malignancies especially in young age (less than 45 years old). However, apart from a few case reports of mucosa-associated lymphoid tissue (MALT) lymphoma, no other H.pylori associated malignancies are reported in children. Screening could be considered for children with first degree relative with gastric cancer at a young age. As they would have similar genetic makeup and environmental exposure to their relatives and eradication of H.pylori if detected may prove to be beneficial. Iron deficiency anaemia is commonly seen in children with poor socioeconomic conditions and dietary inadequacy. Oral iron therapy has shown to be effective in most of the cases. But iron deficiency anaemia refractory to oral iron therapy needs to be investigated further for an underlying gastrointestinal cause. H.pylori infection needs to
be screened for in addition to coeliac disease and other gastrointestinal disorders. For diagnosis of H.pylori infection, gastric biopsies for histopathology in addition to culture and/or rapid urease test should be obtained in these children. There is no role for antibodies in serum, urine or saliva for diagnosis or confirmation of eradication as specific antibodies can remain positive for months after the infection is resolved. Urea breath test remains a highly sensitive, specific and accurate test for H.pylori infection, but hard to perform in a young child. Stool antigen of H.Pylori is more practical for
children unable to cooperate for the breath test. Urea breath test and stool antigen could be effectively used for confirmation of eradication after therapy.



  1. Test and treat strategy for H.pylori not recommended for children with abdominal symptoms.
  2.  Indications for screening for H.Pylori
    • Refractory iron deficiency anaemia
    • History of first degree relatives with gastric cancers
  3. Stomach biopsies on endoscopy required to confirm a diagnosis
  4. No role of serum antibodies or stool antigen for diagnosis of H.pylori infection.


Author competing interests- no relevant disclosures. Questions? Contact the author on 9340 8355

Reflux and PPI’s in the young


Gastrooesophageal reflux (GOR) in infants and children remain one of the commonest presentations to GP’s and paediatricians. It is characterised by regurgitation of stomach contents (acidic and/or non-acid) in the oesophagus in the absence of any organic features that would suggest the presence of Gastrooesophageal Reflux Disease (GORD). A few children with GORD may need medical therapy (acid-blocking agents, feed thickeners or prokinetic agents) and/or surgical therapy (Fundoplication).


Proton pump inhibitors (PPI) remain the most commonly utilised medical therapy for children with GORD.

Common complications from PPI therapy are an increased risk of respiratory and gastrointestinal infections. There may be an increased predisposition to certain gastrointestinal diseases like coeliac disease, gastric fundic gland polyps and eosinophilic oesophagitis (EoE), for children on PPI’s. Malabsorption of certain vitamins and minerals, (calcium, magnesium, iron and Vitamin B12) and disturbances of the gut microbiome may occur. Cardiovascular, bone and renal complications have also been reported.


GOR in infants is defined as frequent effortless regurgitation of feeds. It causes anxiety in parents but resolves in almost 90% of children by 12 months of age. Detailed history to rule out any red flag signs such as bile stained vomiting, hematemesis, unexplained feeding difficulties, blood in stool/Malena, faltering growth, distressed behaviour and any other systemic features are needed. There is enough evidence to suggest that the crying time of an infant is not related to GOR nor can it be reduced with PPI therapy.


Effective management of GOR requires repeated and confidence reassurance. Simple and cheap interventions such as minor feed modifications or thickening agents should be used for infants and where possible avoid the use of PPI’s. However, special consideration needs to be given for infants with a history of back arching (Sandifer’s syndrome), premature birth, repaired congenital diaphragmatic hernia, repaired oesophageal atresia, recurrent aspiration pneumonia, frequent otitis media, episodic apnoea, or neuro-disability. This group warrants further investigation and referral to a specialist physician.


Gastro-oesophageal reflux in children and adolescents needs further assessment to rule out other diseases especially EoE. History of dysphagia, food bolus impactions, retrosternal or epigastric discomfort, hematemesis, melena, unexplained iron deficiency anaemia and symptoms refractory to acid-suppressive therapy helps differentiate functional dyspepsia/GOR from GORD or other oesophageal diseases. Those on chronic, difficult to wean, PPI therapy may need by further investigations such as an endoscopy.


Author competing interests- no relevant disclosures. Questions? Contact the author on 9340 8355