title: Nephrotic-Range Proteinuria and Peripheral Edema in a Child: Not Only Idiopathic Nephrotic Syndrome.
abstract: Hemolytic uremic syndrome (HUS) is defined by the simultaneous occurrence of hemolytic anemia, thrombocytopenia, and acute kidney injury due to thrombotic microangiopathy (TMA) mainly occurring in renal and cerebral microvessels. Although the most common cause of HUS in children is Shiga toxin-producingEscherichia coli, atypical forms in which Shiga toxin is not the trigger may occur. Research over the last few years has shown that complement dysregulation secondary to mutations of genes coding for proteins involved in the regulation of the alternative pathway of complement account for most forms of atypical HUS (aHUS). Among these, thrombomodulin (THBD) gene mutations, representing 3-5% of all alternative pathway complement component abnormalities, correlate with early disease onset and rapid evolution to end-stage renal failure. aHUS onset is generally sudden, but occasionally the only manifestations of renal TMA are arterial hypertension, proteinuria, and a progressive increase in serum creatinine. Nephrotic syndrome at disease onset is exceptional. We describe the case of an adolescent female who presented with peripheral edema due to nephrotic-range proteinuria with bioptic evidence of TMA. Study of the alternative complement pathway showed a heterozygous missense THBD gene mutation (P501L variant) consistent with aHUS diagnosis. One year later she developed clinical signs of hemolytic anemia. Eculizumab, an anti-C5 monoclonal antibody, was started with rapid improvement. This case report highlights the phenotypic variability in aHUS due to THBD gene mutation. Early diagnosis by renal biopsy followed by genetic screening is required to optimize management in such a rare disease with a severe prognosis.
authors.affiliation: Division of Pediatrics, Department of Clinical and Experimental Medical Sciences, University Hospital of Udine, Udine, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Dolcemascolo
authors.affiliation: Division of Nephrology and Dialysis, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Vivarelli
authors.affiliation: Division of Nephrology and Dialysis, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Colucci
authors.affiliation: Department of Laboratories, Pathology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Diomedi-Camassei
authors.affiliation: Istituto di Ricerche Farmacologiche Mario Negri, Clinical Research Center for Rare Diseases Aldo e Cele Daccò, IRCCS, Bergamo, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Piras
authors.affiliation: Istituto di Ricerche Farmacologiche Mario Negri, Clinical Research Center for Rare Diseases Aldo e Cele Daccò, IRCCS, Bergamo, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Alberti
authors.affiliation: Division of Nephrology and Dialysis, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Emma
keywords: Alternative complement pathway; Arterial hypertension; Atypical hemolytic uremic syndrome; Eculizumab; Hemolytic anemia; Nephrotic-range proteinuria; Thrombomodulin gene mutation; Thrombotic microangiopathy