Atypical HUS

Most Haemolytic Uraemic Syndrome is associated with a diarrhoeal illness (D+ HUS), esp E coli O157.

Atypical HUS is a bad name for HUS that develops in certain individuals due to a genetic, complement disorder.  Disease is typically triggered by infection, esp respiratory tract, else diarrheal illness in 80% of pediatric forms.

Consider in young infants (less than 5% of D+HUS cases occur before the age of 6 mo), severe cases, non-colitis.

The penetrance of the disease among carriers of mutations in CFH, CFI and MCP genes is approximately 50%-60%.

Low C3 levels are a clue (seen with mutations in CFH, CFI and MCP).  In almost all cases of aHUS C4 levels are normal. Normal C3 levels do not however exclude a mutation.  Check factor H and factor I too.

Diagnosis

Measure CFH, CFI and MCP levels using radio-immune-diffusion assay (RIDA) or FACS. This however fails to detect low protein levels in 25%-75% of mutations, so genetic analysis also needed.

Check ADAMTS13 activity (as seen in thrombotic thrombocytopaenic Purpura, TTP) as part of differential.

Make sure you have enough blood samples before plasma exchange!

In neonates, screen for defective cobalamin metabolism (excess homocystine and methylmalonate in urine ).  These babies have high mortality from multiorgan failure, a prompt diagnosis and B12 supplementation is their only hope.

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