Table 7 Clinical presentation of the various subgroups of hemolytic uremic syndrome and thrombotic thrombocytopenic purpura and investigations to confirm diagnosis
Age at onset and clinical presentation | Probable diagnosis | Investigations to confirm diagnosis |
|---|---|---|
Neonatal period Severe jaundice Porto colour urine without major hematuria Consanguineous family and/or similar symptoms or neonatal death in siblings | Congenital TTP (Upshaw-Schulman syndrome) | ADAMTS 13 deficiency (< 10%) without anti-ADAMTS 13 antibobies Mutation in ADAMTS13 (autosomal recessive) |
Neonatal period-< 6 months Failure to thrive, feeding difficulties, hypotonia ± developmental delay Consanguineous family | Methyl-malonic aciduria-associated HUS | Hyperhomocysteinemia, hypomethioninemia, methyl-malonic aciduria Mutation in MMACHC (autosomal recessive) |
< 2 years Fever Invasive S.pneumoniae infection (proven or suspected): pneumonia, meningitis, septicaemia, especially if empyema or subdural collection | HUS due to Streptococcus pneumoniae | False positive Coombs test Positive cultures (blood, CSF) or PCR Positive T-activation test (exposure of the Thomsen-Friedenreich antigen on red blood cells) supports the diagnosis |
> 6 months-5 years Diarrhea ± melena during the last 2 weeks Endemic region of STEC or Shigella dysenteriae infection | STEC-HUS (Shigella dysenteriae- HUS in endemic regions) | Stool or rectal swab: culture for STEC (Mac Conkey for 0157:H7); PCR for Stx Serum: anti-LPS antibodies against the most common serotypes in the local country |
Adolescents and adults Fever Central nervous system manifestations No or mild renal involvement Autoimmune context (SLE, APLS, thyroiditis) | Immune TTP | ADAMTS 13 deficiency (< 10%) with anti-ADAMTS13 antibodies |
From birth to adolescence and adult age No prodromic diarrhea or prodromic diarrhea but any of the following: - age < 6 months or > 5 years - insidious onset - relapse of HUS - suspicion of previous HUS - previous unexplained HUS - post-transplant HUS - pregnancy (post-partum) HUS - non synchronous familial HUS | Complement-aHUS | Complete investigation of the complement system |