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

HUS, hemolytic uremic syndrome; TTP: thrombotic thrombocytopenic purpura; ADAMTS13: A Desintegrin And Metalloproteinase with a ThromboSpondin type 1 motif, member 13; MMACHC: methylmalonic aciduria and homocystinuria; CSF: cerebro-spinal fluid; PCR: polymerase chain reaction; STEC: Shiga-toxin producing Escherichia coli; Stx: Shiga-like toxin; LPS: lipopolysaccharide