ESPN 51th Annual Meeting

ESPN 2018


 
Typical hemolytic uremic syndrome cohort screened for genetic complement abnormalities
Serena Ascione 1 Valentina Bruno 1 Alfonso Ferretti 1 Angela De Luca 1 Gabriele Malgieri 1 Gaia Scavia 2 Elena Bresin 3 Marina Noris 3 Carmine Pecoraro 1

1- NEPHROLOGY AND DIALYSIS UNIT, SANTOBONO CHILDREN HOSPITAL, NAPLES, ITALY
2- DEPARTMENT OF FOOD SAFETY, NUTRITION AND VETERINARY PUBLIC HEALTH, ISTITUTO SUPERIORE DI SANITĂ , VIALE REGINA ELENA, ROME, ITALY
3- IRCCS-ISTITUTO DI RICERCHE FARMACOLOGICHE "MARIO NEGRI," CENTRO DI RICERCHE CLINICHE PER LE MALATTIE RARE "ALDO E CELE DACCò," RANICA BERGAMO, ITALY
 
Introduction:

Complement hyperactivation leads to endothelial damage and microvascular thrombosis, and plays a role in typical and atypical HUS.We describe our cohort of hemolytic uremic syndrome (HUS)-patients screened for genetic complement abnormalities, hence its role is, currently, widing.


 

Material and methods:

We studied our typical-HUS patients, in years 2015-2017, with univariate analysis detecting differences in phenotype, STEC-serotype, complementemia, genotype. Genetic complement screening was achieved with next generation sequencing (NGS).


 

Results:

20 HUS patients (16Female– 4Male), mean age: 4.5 years. Neither familial- nor secondary-HUS. Gastrointestinal presentation and oligoanuria in all; 1(5%) with respiratory symptoms, 5(25%) neurologically involved, 12(60%) hypertensive, 3(15%) needed ICU, dialysis necessary in 17(85%) and lasted ≥7 days in 4(20%). STEC-serotype: O157 in 5(25%); O111 in 5(25%); O26 in 4(20%); O121 in 1(%); O145 in 1(5%); unknown in 4(20%). Hypocomplementemia in 5(25%). Six-months follow-up showed CRF in 3(15%), 2(15%) hypertensive. NGS showed polymorphisms involving CFH and MCP genes in 18/20. CFH-gene: c.332C>T in 4(20%) in heterozygosis; 1(5%) in homozygosis; c.332C>T, c.2016A>G, c.2808G>T 4(20%) in heterozygosis (1 with E.Coli O157). MCP-gene: c.897 T>C in 6(30%) in heterozygosis (2 E.Coli O157, 2 E.Coli O111). CFHgene + MCPgene: c.332C>T in heterozygosis + c.897T>C in heterozygosis (1 E.Coli O111)

 

Conclusions:

We suggest multifactorial disease model -gene environment interaction- to understand mechanisms beneath HUS. All our patients, as typical HUS, have gastrointestinal presentation, and most of them showed polymorphisms of MCP and CFH genes and STEC serotypes. Polymorphisms appear of unclear meaning in terms of natural history of HUS. We suggest extending NGS to all HUS patients and a long, strict follow up, to correlate genetic abnormalities to a worst long term prognosis.