Presentation: Child with atypical haemolytic uraemic syndrome

A three-year-old boy presents with a one-week history of peripheral oedema and periorbital puffiness after a recent diarrhoeal illness. Examination reveals hypertension, generalised oedema, haematuria and proteinuria together with anaemia, thrombocytopenia and acute renal failure. Further investigations reveal low complement levels.

Genetic atypical hemolytic-uremic syndrome (aHUS) should be suspected in individuals with a diagnosis of aHUS (known environmental precipitants excluded) if:

• they have experienced recurrent episodes; and/or
• there is a positive family history of aHUS in an individual or individuals where environmental triggers have been excluded; or if there is parental consanguinity, raising the possibility of an autosomal recessive form.

• Consult the National Genomic Test Directory. Here you can access the rare and inherited disease eligibility criteria document for information about individual tests and their associated eligibility criteria. You can also access a spreadsheet of all available tests.
  • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see our Knowledge Hub resource ‘Genomic testing in the devolved nations’.
  • To find out which genes are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed-Off Panels Resource.
• R201 Atypical haemolytic uraemic syndrome: Likely to be the most suitable indication for your patient. This includes a small panel and multiplex ligation-dependent probe amplification (MLPA).
• Other relevant indications are:
  • R240 Diagnostic testing for known mutation(s): This indication can be used for someone who is clinically affected by aHUS if a member of the family already has a known pathogenic or likely pathogenic gene variant(s). In this situation, the laboratory will only test for the known familial variant(s).
  • R242 Predictive testing for known familial mutation(s): This is for a predictive (also known as presymptomatic) test and should be used for anyone who is clinically unaffected but has a relative with a pathogenic or likely pathogenic variant(s). It must be requested by clinical genetics.
• The tests listed above do not include whole genome sequencing (WGS). For these tests:
  • You can use your local Genomic Laboratory Hub (GLH) test order and consent (record of discussion) forms.
  • Parental samples may be needed for interpretation of the proband’s result, for example to determine whether a variant is de novo or inherited. These samples may be requested by the testing laboratory or you may wish to contact clinical genetics.
• Note that different forms are required for any test involving WGS.
• These tests are DNA-based, so an EDTA sample (purple-topped tube) is required.

For clinicians

• Atypical HUS
• Genomics England: NHS Genomic Medicine Service (GMS) signed off panels resource
• NHS England: National Genomic Test Directory

For patients

• Atypical HUS: What is Atypical HUS?