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. From here you can access the rare and inherited disease eligibility criteria 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 Genomic testing in the devolved nations.
• For information about the genes that are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• R201 Atypical haemolytic uraemic syndrome is 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 variant(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 variant(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.
• None of the tests outlined above use whole genome sequencing (WGS), so you should use your local Genomic Laboratory Hub test order form and consent (record of discussion) forms.
• Note that different forms are required for any test involving WGS.
• Parental samples may be needed for interpretation of the child’s result. Parental samples can be taken alongside that of the child, and their DNA stored, or can be requested at a later date if needed.
• Most tests are DNA based, and an EDTA sample (typically a purple-topped tube) is required. There are a few tests for which a different type of tube is used; see Samples for genomic testing in rare disease.
• If you are discussing genomics concepts with your patients, you may find it helpful to use the visual communication aids for genomics conversations.
• Information about patient eligibility and test indications were 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

• 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?
• Kidney Research UK: What is atypical haemolytic uraemic syndrome (aHUS)?