A screening strategy for Coeliac disease in children and young people with Down Syndrome

Paediatric guidelines (in development)
NHS Lothian

Objectives

This guidance is intended for clinicians and health care professionals in Lothian who are involved with the care of children and young people (YP) with Down Syndrome (DS) and to inform discussion regarding the need for screening for Coeliac disease (CD) which is recognised as an ‘at-risk’ condition by specialist organisations and to offer options for how and when to offer testing/ screening for the condition after counselling of a family. It also advises what options there are for testing and what opportunities there are for timing of testing.

Scope

This guidance is intended for children and young people with DS under age 18 in NHS Lothian

Audience

All secondary health care professionals dealing with children and YP under 18 with Down Syndrome

Roles and Responsibilities

Clinicians dealing with patients with DS, primarily the community paediatrics team, should be aware of the association and discuss the condition with families and to inform them of risk and potential for development of CD as part of the management of children and young people with DS in the context of other healthcare issues (eg thyroid screening). All should be prepared for a discussion about CD, when appropriate and to seek further advice as required from the coeliac service and to utilise opportunities to discuss screening for the condition at appointments as part of a healthcare assessment and clinical reviews.

Why should we screen for Coeliac Disease in Down syndrome and when?

We know that in the general population, the prevalence of coeliac disease is estimated to be 1:100 in the UK if we were to screen the population, but this is not currently advised. ESPGHAN recommendations 2012 and 2020 detail at-risk patients 1,2. However, BSPGHAN3 (British Society of Paediatric Gastroenterology, Hepatology and Nutrition) and NICE4,5 recommend there should be a low threshold for investigating children with associated (‘at-risk’) conditions, as it is recognised that many cases remain undiagnosed.

Associated conditions include (estimated lifetime prevalence):

  • Type I diabetes (≥ 8%)
  • Selective IgA deficiency (1.7%–7.7%)
  • Down Syndrome (5%–12%)5-7
  • Williams Syndrome (8.2%)
  • Turner Syndrome (4.1%–8.1%)
  • Autoimmune thyroiditis (∼15%)
  • Autoimmune liver disease
  • Unexplained raised transaminases without known liver disease
  • Intussusception
  • Dermatitis herpetiformis
  • Relatives of coeliac patient: – First-degree relative (∼10%) – HLA-matched sibling (∼30%–40%) – Monozygotic twin (∼70%)

Current Guidance and BSPGHAN Flowchart

Information from BSPGHAN 2013

Information from BSPGHAN 20133

The BSPGHAN coeliac disease working group modified the then ESPGHAN 2012 guidance with advice in asymptomatic children with an associated condition to consider HLA typing as well as standard serology. If an individual is HLA DQ2/DQ8 positive: continue surveillance (optimum frequency for repeat blood testing unclear, but every 3 years is reasonable if asymptomatic) and perform endoscopy if symptomatic. If HLA DQ2/DQ8 negative: development of CD highly unlikely. Discontinue regular antibody screening but clinical review if suggestive symptoms develop.

Information from NICE NG 20 AND QS 134

Information from NICE NG 20 AND QS 134 4,5

NICE guidance has no clear messaging on DQ testing as they did not consider the current guidance from ESPGHAN or BSPGHAN at the time. For DS, NICE states in NG 20 (2015) to ‘consider’ serological testing4. This is a less strong recommendation. They then published a Quality Standard QS 134 in 2016 that stated : 1: serological testing in coeliac disease suggests, healthcare professionals offer a serological test for coeliac disease to people at ‘increased risk’ or with symptoms of coeliac disease and ensure that people have been following a gluten-containing diet for at least 6 weeks before the test5.

NICE NG20 - People deemed at increased risk or with symptoms of coeliac disease

  • persistent unexplained abdominal or gastrointestinal symptoms
  • faltering growth
  • prolonged fatigue
  • unexpected weight loss
  • severe or persistent mouth ulcers
  • unexplained iron, vitamin B12 or folate deficiency
  • type 1 diabetes, at diagnosis
  • autoimmune thyroid disease, at diagnosis
  • adults who meet the irritable bowel syndrome diagnostic criteria
  • first-degree relatives of people newly diagnosed with coeliac disease

Recognition of coeliac disease

Offer serological testing for coeliac disease to:

• people with any of the following:

  • persistent unexplained abdominal or gastrointestinal symptoms
  • faltering growth
  • prolonged fatigue
  • unexpected weight loss
  • severe or persistent mouth ulcers
  • unexplained iron, vitamin B12 or folate deficiency
  • type 1 diabetes, at diagnosis
  • autoimmune thyroid disease, at diagnosis
  • irritable bowel syndrome (in adults)

• first-degree relatives of people with coeliac disease.

 

Consider serological testing for coeliac disease in people with any of the following:

• metabolic bone disorder (reduced bone mineral density or osteomalacia)

• unexplained neurological symptoms (particularly peripheral neuropathy or ataxia)

• unexplained subfertility or recurrent miscarriage

• persistently raised liver enzymes with unknown cause

• dental enamel defects

• Down syndrome

• Turner syndrome

HLA typing for coeliac disease in Down Syndrome and its utility

The suggested management approach from BSPGHAN for asymptomatic cases in ‘at-risk’ individuals has been modified and applied specifically to individuals with DS and is in current guidance. Human Leukocyte Antigen (HLA) genes are often associated with certain conditions. They are also known as disease association antigens (or more accurately, permissibility antigens).

People with coeliac disease are known to have one or more of HLA DQ 2.5 (commonest), HLA DQ8 (less common) or HLA DQ2.2 (least common) and are often found in combination in 99.6% of known CD patients6. Having that ‘genetic factor’ might mean that you may develop coeliac disease in your lifetime, but it does not mean that you will definitely develop it. The risk of developing coeliac disease without one of these HLA types is very rare and less than 1%. A negative test is therefore very helpful. A positive result can allow some degree of risk stratification.

We are not the first group to propose DQ typing, it has been detailed by teams from the Netherlands in 2000 and in 20097. This presents an opportunity for coeliac screening in Children with DS as they are a little more likely to carry the DQ type (around 60%) than the general population which is up to 40% of the population. This means that those ‘at risk’ and who carry a permissibility antigen may have a risk of approximately 10% of developing the condition but means that the vast majority who carry the ability will not develop CD. Data from NHS Lothian and Fife, suggests up to 40% of children and young people with DS could be eliminated from long-term coeliac serology screening8,9.

DQ typing does not require exposure to a gluten containing diet and therefore testing could be performed in early life prior to serology and can be performed as an isolated test, or in combination with serology in a gluten exposed individual. This testing should be discussed with families and testing offered as part of an ‘opt-in’ plan, given that this testing and its implications needs to be understood by the families and the option not to be tested at all is entirely valid.

The DQ test is sent to the Blood Transfusion Service (BTS) HIE laboratory RIE, 2mls minimum EDTA. It is a paper request and form in Lothian and is part of this guideline, see HLA typing form. This is available from the phlebotomy rooms at RHCYP. Results are now uploaded to SCI store by the lab but will not appear on your results workbench.

Standard serology testing for coeliac disease

Coeliac serology testing (a coeliac screen) is standard practice in symptomatic patients suspected to have the condition in gluten exposed individuals. Clearly if a patient is symptomatic, testing at any age over 6 months may be helpful but if asymptomatic the earliest we would screen would be in the 2nd year of life, for example at over 12 months of age. This is a venous blood test which is sent in NHS Lothian to Biochemistry labs at WGH (serum, gel tube 1ml minimum). This can be done along with other relevant bloods eg TFTs and other bloodwork. In Lothian a Total IgA level is not required (unless there is a specific reason) due to an automatic system where Total IgA is performed of the TTG IgA is below 0.6 g/L and a TTG IgG will automatically be performed if the Total IgA level is below 0.2 g/L.

Editorial Information

Last reviewed: 08/05/2024

Next review date: 10/05/2027

Author(s): Consultant Gastroenterologist NHS Lothian, RHCYP, ST8 in Paediatrics, Community Paediatrics, NHS Lothian, RHCYP, Clinical Director, Community Paediatrics NHS Lothian, RHCYP , Service Development Lead, Community Paediatrics Lothian, SJH.

Approved By: Medical Guidelines Committee

Related resources

Definitions

Down Syndrome (DS) – all Individuals with Trisomy 21

Coeliac disease (CD) – an autoimmune enteropathy in a genetically susceptible individual, dependent on gluten (wheat, barley, rye) and which reverses on a Gluten Free Diet (GFD)

DQ typing – HLA testing via Blood Transfusion Service (BTS) Tissue typing laboratory

Screening – a process of actively checking for a condition in a group of patients seen as at increased risk

References

1.Husby S, Koletzko S, Korponay-Szabo IR, et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. Journal of Pediatric Gastroenterology and Nutrition. 2012;54:136-60.

2.Husby S, Koletzko S, Korponay-Szabó I, et al. European society paediatric gastroenterology, hepatology and nutrition guidelines for diagnosing coeliac disease 2020. J Pediatr Gastroenterol Nutr 2020;70:141–56.

3. Murch S, Jenkins H, Auth M, et al. Joint BSPGHAN and Coeliac UK guidelines for the diagnosis and management of coeliac disease in children. Archives of Disease in Childhood. 2013;98:806-11.

4. NICE Coeliac disease: recognition, assessment and management (NG 20, 2015) https://www.nice.org.uk/guidance/ng20 Accessed 14.1.24

5. NICE Coeliac disease: Quality Standard (QS 134, 2016) https://www.nice.org.uk/guidance/qs134 Accessed 14.1.24

6. Tye-Din JA, Cameron DJ, Daveson AJ, et al. Appropriate clinical use of human leukocyte antigen typing for coeliac disease: an Australasian perspective. Intern Med J 2015;45:441-50

7. Wouters J, Weijerman ME, van Furth AM, et al. Prospective human leukocyte antigen, endomysium immunoglobulin A antibodies, and transglutaminase antibodies testing for celiac disease in children with Down syndrome. J Pediatr. 2009. 154(2):239-42

8. Sumner C, et al. G368 DQ typing is effective in coeliac disease screening in children and young people with down syndrome in South East Scotland. Archives of Disease in Childhood 101 (Suppl 1): A215.2-A216. Oral presentation at RCPCH Liverpool April 2016.

9. Lewis T, et al. HLA-typing as cost effective screening test for coeliac disease in children with Down Syndrome. Frontline Gastroenterology. 13 (Suppl 1): A3-A4. Oral presentation at BSPGHAN Birmingham April 2022.