Presentation: Child with incidental hyperglycaemia

A 10-year-old boy was recorded as having a raised random blood glucose level (13 millimoles per litre (mmol/L)) when attending his local emergency department after an accident. This was subsequently rechecked, and his fasting glucose was 6.8mmol/L, with an HbA1c of 50 millimoles per mol (mmol/mol). His father had previously been recorded has having a slightly raised glucose level during a routine medical, and had been told that he had borderline diabetes, but was not on any treatment. The boy’s paternal grandfather was diagnosed with type 2 diabetes in middle age and was on metformin, with an HbA1c of 48mmol/mol–60mmol/mol.

• Two or more episodes of incidental hyperglycaemia in children should alert you to the possibility of glucokinase maturity onset diabetes of the young (GCK MODY).
• Flags for an underlying genomic cause of GCK MODY include:
  • asymptomatic stable fasting hyperglycaemia (5.5mmol/L–8mmol/L), with a minimum of two independent laboratory fasting blood glucose test results; and
  • an HbA1c of 36mmol/mol–58mmol/mol (5.5%–7.5%).

• Consult the National Genomic Test Directory. From here you can access the rare and inherited disease eligibility criteria, which provides information about individual tests and their associated eligibility criteria. You can also access a spreadsheet containing details of all available tests.
  • For those working within NHS Wales, please consult the All Wales Medical Genomics Service website for information on how to arrange testing.
• To find out which genes are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• Decide which of the panels best suits the needs of your patient or family.
  • R142 will test for GCK MODY only. If the phenotype is less obvious, R141 will test for GCK MODY alongside other MODY genes. If you are not sure which is the most appropriate test, a laboratory scientist will make the decision according to the information you provide.
• An EDTA sample is required for DNA testing, along with a completed referral form.
• Look for mild, stable hyperglycaemia in a parent. GCK MODY is inherited in an autosomal dominant pattern, meaning that each child has a 50% chance of inheriting the same genetic change if even one parent is affected.
• If neither parent is known to have diabetes or a raised blood glucose, a fasting glucose should be organised for both parents. Testing other unaffected relatives is not essential, but can be offered if requested. An HbA1c test is recommended in addition to testing for the GCK variant.
• Bear in mind that due to the mild hyperglycaemia seen in GCK MODY, other family members may also have been picked up incidentally (often, women are first identified during routine screening in pregnancy).
• If there is a history of diabetes on one side of the family, that parent should be tested initially. If a fasting glucose of 5.5mmol/L–8mmol/L is detected, the parent should also be referred for genomic testing for GCK MODY.
• Information about patient eligibility and test indications was correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

For clinicians

• DiabetesGenes: What is Glucokinase (GCK)?
• NHS England: National Genomic Test Directory

For patients

• DiabetesGenes: What is Glucokinase (GCK)?